ラット食道の蠕動運動を制御する神経回路に関する研究

Title

ラット食道の蠕動運動を制御する神経回路に関する研究( 本

_{文(Fulltext) )}

Author(s)

嶋, 剛士

Report No.(Doctoral

Degree)

博士(獣医学) 甲第450号

Issue Date

2016-03-14

Type

博士論文

Version

ETD

URL

http://hdl.handle.net/20.500.12099/54523

※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。

cg̈ː3ʍãˎãJ×ŭ!Fȵɗďʺ2˪!FȭȽ

̛̙̞̚Ř

ʼn˭ħIJħIJ˱

ˊùȇåIJȭȽȷ

̓ʼn˭ħIJ̔

ō
Û

ģ

2

Ƞ

Ƞ
Ǘ

Ȗʩ‡ʚ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪3 ɡʭ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪4 Ķ̌ƺƥC7Ķ̌ƨǣ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪7 Ʉ1 Ɂ Ƨʘ in vivo Ķ̌ɎJȏ'cg̈ːʍãˎã3ʜƿ ɡʝ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪15 ɘǀ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪19 ɪĻ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪27 Ʉ2 Ɂ ̈ːʍãˎã2Ľ!FRsZM[„Żñŵȵɗ3Ɗ+ʬɉȝ1ŨÞ ɡʝ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪30 ɘǀ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪31 ɪĻ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪38 Ʉ3 Ɂ ̈ːǔɐɆˎã2Ľ!FRsZM[„ŻñŵŅƀȵɗďʺ3Ŷŕȝǖɴ3njʟ ɡʝ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪42 ɘǀ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪44 ɪĻ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪53 ɠùɪĻ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪56 ʮˀ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪59 ƤȆ̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪̪60

Ȗ

Ȗ

ʩ ‡ ʚ

SḌstandard deviation̓ǒǵºŐ̔

L-NAMẸNG_{-nitro-L-arginine methyl ester}

TRPV1̣transient receptor potential cation channel, subfamily V, member 1 NỌnitric oxide̓‡˛äȿɒ̔

4

ɡ

ɡ

ʭ

ǬäɈ3ʍãˎã4̗ÉĹȂJó¼Dɭ˦¼:ȹˆ!F'?3ˎãǑŝ.F 3ʍãˎã4̗ǬäɈJǐſ!FɤʸɆ/ʽʸɆ3æʬG'ïɥ…Šɣ2C*-ʹF̓Furness, 2006; Hansen, 2003; Leonard et al., 2006; Olsson and Holmgren, 2011̔ ɰDɭ˦2ʂF=.3ǬäɈ3Ɇň4ŗǷɆ.ǐſG-E̗%3ˎã 4ġÉ2İĖ!Fțˑ'ÉĖȵɗɎ2C*-×ŭG-F̓Furness, 2006; Hansen, 2003; Leonard et al., 2006; Olsson and Holmgren, 2011̔ ɈɺÉĕ3‰Ƭ ADŽ̋ɒ3ǨÅ2CEŻʙȵɗØǻGF/̗ɌɿŠȵɗò…Ɇ˩ȵɗò2İĖ! FšĖȵɗJˇ -ˎãȵɗǧŵäGF/Ņƀȝ1ȵɗďʺ2C*-̗ȄǢ 2ùʃ'˓Ò1ˎãŞʹGF̓Furness, 2006; Hansen, 2003; Leonard et al., 2006; Olsson and Holmgren, 2011̔ 3C1ÉĖȵɗɎ2CF×ŭ4̗Žǁ ȵɗɎ/ÒE˸G'Ȅż.*-@̗ǖɴF %3'?̗ŁɻAħɻ3ʍãˎ ã4̗¨ĥ2ƙÏG'ǒƹ2-@ʨț!F/ôɴ.F̓Ciccocioppo et al., 1994; Onori et al., 2003; Shiina et al., 2005; Smith and Robertson, 1998; Suzuki et al., 1994; Waterman and Costa, 1994̔

‡ƨ̗̈ː3Ɇň24ǔɐɆ.ǐſGF˖¦İĖ!F ̈ːǔɐɆ˖2F ̈ȂC7ǭ¨3ȹˆ4̗Ŝ̎JŽǁ/'˅ʸ-˅ʸȵɗîľ/ĥƽŵ3ȵɗď ʺ2CE×ŭG-F/ȩDG-F̓Andrew, 1956; Clouse and Diamant, 2006; Cunningham and Sawchenko, 1990; Goyal and Chaudhury, 2008; Jean, 2001; Lu and Bieger, 1998; Neuhuber et al., 2006̔ ŽǁȵɗɎˎã×ŭ3¨/1*-F/4̗Žǁ/3ˊəJɜ*'̈ːƙÏǒƹ2-̗Ɲ˗ȵɗ.F˅ʸȵɗ J˺ǟØǻ-@șɥǑ3ïɥîŲʹF3>.̗ȂʶJȹˆ!FʍãˎãǑ3î Ų4ŞʹG1/D@ƭD.F̓Shiina et al., 2013̔
3C2̗̈ːǔɐɆ3ˎã×ŭ2Žůȝ1ŨÞJǀ'!34̗ĥƽŵ3ȵɗ. F ̗̈ːǔɐɆ˖2-@țˑ'Ɇ˩ȵɗòİĖ!F/ƭD 2G-E̗Ņƀ3ȵɗďʺˎã×ŭ2ĺŒ-F/ȱĉG-F ť

żIJȝ1ȭȽ2CE̗˅ʸȵɗ/̈ːǔɐɆ3ȵɗɆƒù˖2̗ÉĖȵɗ3ɕƸú Ư2Ɲ˗-F/ȱG-E̗ÉĖȵɗ˅ʸȵɗ2CFˎã×ŭJµ̊! FôɴŵȱĉG-F̓Neuhuber et al., 2006; Wörl and Neuhuber, 2005̔ ‡ ƨ̗ǖɴIJȝ1ȭȽ/-̗˃Ř̗RsZM[„JȵɗØǻʌ/-ȏ'ȭȽě ĀG-F̓Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2006; Shiina et al., 2012̔ RsZM[„4ĊʿĮ2þ=GFʖ1ʿ>ſÑ.̗ ‡ǗŻʙȵɗ2țȊ-FMQ„b}kĘñŨtransient receptor potential cation channel, subfamily V, member 1̓TRPV1̔2ªȏ-ȵɗɔɲJʄĩ#F /ȩDG-F̓Holzer, 1988; Holzer, 1991; Holzer, 2004; Geppetti and

Trevisani, 2004; Tominaga and Tominaga, 2005̔ ƙÏ'̈ːǒƹ2-˅ʸȵ ɗØǻ2CEʨțG'ǔɐɆïɥîŲRsZM[„ƅŒ2CEƄ×G'/ D̗̈ːǔɐɆ˖24̗RsZM[„ŻñŵȵɗJþK(ŅƀȵɗďʺİĖ̗̈ ːǔɐɆˎãJƄ×ŵ2Ɲ˗-F/ƭD21*-F̓Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2012; Shiina et al., 2006̔
ž‰3C2̗̈ːǔɐɆˎã2Ľ-̗©D3ǖɴJǀ'!/ȱĉG-FÉĖȵɗɎ.F̗03C1ŨÞJǀ'-F3ʥɔ24I*-1  ȃ2̗ƙÏǒƹ.4ʜƿ!F/.1̈ːʍãˎã2Fǖɴ4Ʒʜƭ 3==.F
%.ƹȭȽ.4̗̈ːǔɐɆ˖3ʍãˎã2Ľ-̗ÉĖȵɗJþK(ȵɗďʺ 03C1×ŭJʏ*-F3JƭD2!F/JȠȝ/' ȃ2̗RsZ M[„Żñŵȵɗ/ÉĖȵɗɎDǐſGFŅƀȵɗďʺ3ǖɴȝŨÞ3ʜƭJȠ Ƌ' Ʉ̚Ɂ.4̗in vivo .̈ːˎãJʤ¯!FĶ̌Ɏ3ȰɀJʏ*' Ʉ̛Ɂ. 4̗Ȱɀ'in vivo ̈ːˎãdzĵɎJȏ-̗RsZM[„ŻñŵŅƀȵɗďʺ24 ̈ːʍãˎãJ×ŭ!FǖɴF/JƭD2' D2Ʉ̜Ɂ.4̗ƙÏ '̈ːǒƹJȏ'in vitro Ķ̌Ɏ2CE̗RsZM[„ŻñŵȵɗȯĢcgC7

6

ǿÎɧcgȐƽ3ǒƹ3ïɥîŲJǞʼ̗RsZM[„ŻñŵŅƀȵɗďʺ3Ŷ ŕȝ1ŨÞJnjʟ'

Ķ

Ķ̌ƺƥC7Ķ̌ƨǣ

̓ ̚ ̔ Ķ ̌ ã Ȃ

14̩17 ˋ̒3 Wistar Ɏ˷cg̓400-600 g̣™•Ķ̌ãȂ̗Ěȉ̗ƫƹ̔='4 10̩12 ˋ̒3 Sprague-Dawley Ɏ˷cg̓300-350 g̣ƫƹ SLC̗˼Ŋ̗ƫƹ̔J ȏ' ̉ɯķ3Dzś422 ± 2 2ʬɉ̗ƭƱāƵ 12 Ư˩̣12 Ư˩̓ƭƵ 7̣00 19̣00̔3Ȍğ.̉ɯ' ̉ɯƵ˩Ž4ǠːǠ/őʳēť̉ƥ̓LABO MR Stocḳ ƫƹˁȎʔ̗ǔǩ̗ƫƹ='4MF̣Q€O„a˚ǝ̗ƾ—̗ƫƹ̔JʁȐ2Ƙð #'
ƹȭȽ2FãȂĶ̌4!;-̗ʼn˭ħIJŲȏȍȂȷIJ˖ãȂĶ̌ļǃĬć¢ .ļǃJñ'Ū2ʢôG'@3.E̗ʼn˭ħIJãȂĶ̌ðƂʘȺ2ū*-ĶƩ ' ̓ ̛ ̔ ʌ Ü  C 7 Ƕ ǭ
̐˘ʌ/-̗M`q„̓ąÃɑʌ̗ħˮ̗ƫƹ̔ĝ˛Way„̓Wa†̣ Ʉ‡ˆÇ̗ƾ—̗ƫƹ̗̔α-Uƒƒ†]̓hRMe]U̗ƾ—̗ƫƹ̗̔N‚a„ ̓ƾ—äſ̗ƾ—̗ƫƹ̗̔u„gmoa†̓`zlu„b̣Çɀʔʌ̗ƾ—̗ ƫƹ̔Jȏ' α-Uƒƒ†]4̗10% 2-Hydroxypropyl--cyclodextrin̓ąÃɑ ʌ̔2Ƕʜ̗ȍȋ̈ĝǠ̓0.9% NaCl̔.œ˜' N‚a„4ȍȋ̈ĝǠ.Ƕʜ '
ƙÏǒƹJȏ'Ķ̌.4̗DŽ̋ǭ/-U‚r]ǭJȏ' U‚r]ǭ3ɖſ 4̗NaCl 118.4 mM, KCl 4.7 mM, CaCl2 2.5 mM, MgSO4 1.2 mM, NaHCO3 25 mM, KH2PO4 1.2 mM, VX†] 11.7 mM .F

RsZM[„̗D-dvU€„̗NG_{-nitro-L-arginine methyl ester̓L-NAME̗̔} N-acetyl-1-tryptophan 3,5-bis (trifuluorometyl) benzyl ester̓L-732,138̔4̗ Sigma-Aldrichȳ (St LouisɋĔ)DʷÅ'

8 ̓ ̓ ̜ ̔ ̐ ˘ Š  c g 2   F ̈ ː ʍ ã ˎ ã 3 dz ĵ ̓in vivo Ķ̌̔ ̓ ̜ ̚ ̔ ̐ ˘
Ķ̌2­!FãȂ4̗ĝ˛Way„C7α-Uƒƒ†]3ǯù̗u„gmo a†çȅ̗N‚a„çȅ3)̗"GJȏ-̐˘JƩ' ĝ˛Way„C7α-Uƒƒ†]3ǯù̐˘̣ĝ˛Way„̓50 mg/kg̔3Ɇɫ Éǥľ2C*-cgJˤ˼ä'Ū̗α-Uƒƒ†]̓40 mg/kg̔Jń˼ɶÉ2 ƅŒ-̐˘' ħɽãɶ2ƎÅ'Ri~†‚̓Ɓʐǣ4Ū˄̔Jš-̗̐ ˘ʌ3ƊɞƅŒJʏ*' ƊɞƅŒ3̐˘ʌ24̗ĝ˛Way„̓5̩7 mg/kg/h̔ /α-Uƒƒ†]̓20̩25 mg/kg/h̔3ǯùǭJȏ' u„gmoa†2CF̐˘̣u„gmoa† 40 mg/kg JɼɺÉ2ƅŒ 'Ū̗̚Ư˩'E714 mg/kg .ħɽãɶCEƊɞƅŒJʏ*' N‚a„2CF̐˘̣N‚a„1.2 g/kg JɼɺÉ2ƅŒ' ̓ ̜ ̛ ̔In vivo ̈ːˎã3ʠˡǣ̓̈ː3ÉɺĕĤãC7Ɠˆ˟3dzĵǣ̔
̐˘JƩ'Ū̗¨Dz4Homeothermic Blanket Systems (Harvard̗Holliston̗ ɋĔ)Jȏ-̗3637˚C 2³*' ħɽ˖ȟɾJÒ˨-ŏ¼ħɽãɶJ˻Ï̗ Ò˨įCEȍȋ̈ĝǠJÂĞ'ĥũ1 mm 3w€Ob‚„ʔRi~†‚JƎÅ ' ħɽãɶ3Ri~†‚Jš-̗ʎĕ3dzĵC7̐˘ʌ3ƊɞƅŒJúƯ2 ʏ*'
̂˖ǘŽÒ˨2CÊ˖̈ːJ˻Ï̗Ć̃ȡŠ2-̈ːāđJÒ˨̗Ò˨į 2ĥũ2.4 mm̘Éũ 1.5 mm 3w€Ob‚„ʔRi~†‚Jɰ¼ƨü2ɏ 5 mm Ǝ Å̗ɍ.ɘɓJ' ‡ƨ̗ɼ˖ǘŽÒ˨2CE˻Ï'ɼ˖̈ː2@̗ɰȡ‰ 2-Ri~†‚J̃¼ƨü2ƎÅ' Ɓʐ2CEƎÅ'̂˖̈ː:3Ri~† ‚24̗ȍȋ̈ĝǠ.Ǵ''[€X„b~†rJƒɞ̗D2̗Dzȍȋ̈ ĝǠ.Ǵ''x€QcgvgJƒɞ' ɼ˖̈ː:3Ri~†‚24ˆƨǧ

DžJȏ-Ñʼn#'[€X„b~†rJƒɞ' Ñʼn#'[€X„b~†r 3Ʀɂ3‡ƨJx€Qcgvg3Ⱦǟó/ú ̏/1FC2ēĵ' Ʀɂ ȡŠ2qP†]g„]f~†Z†2ēĵ's]bcUĹčJɧ̗̈ːïɥ ˎã2C*-ȹˆG'ȍȋ̈ĝǠJďï̗%3Ĺ˟JƓˆ˟/-dzĵ' œƨ3b~†r4̗ĕg„]f~†Z†Jƒɞ̗̈ːïɥˎã2C*-țȍ! FÉɺĕ3ĤäJʠˡ' qP†]g„]f~†Z†C7ĕg„]f~† Z†2ŀÏ'˺ǟ´ö4̗r€c\L„s̓AD Instruments̗Bella Vista NEW̗ Q†]g€L̔Jš-̗Power Lab System̓AD Instruments̔2-ʠˡ' ̓Ē̔̚
̈ːïɥˎãJțȊ#F'?̗x€Qcgvg3ǭ˾J‰Ƭ#F/.É ɺ:/ĕØǻJá' ̈ːÉɺ:3ĕØǻ3Ư˩430 ȸ=./̗øØǻƯ˩3 ˩24Ƴ§15 Ñ3ǿáĕƯ˩Jʡ' Øǻ3ţ4x€Qcgvg3ǭ˾3‰ Ƭ¹2ĽŲ!FǠĕ (mmHg) /-ȱ'
='̗ʎĕ4̗ħɽãɶ:3Ri~†‚Jĕg„]f~†Z†:ŀ̗dzĵ '
Ķ̌ɕ‘Ū̗cg4ʃǚ˟3u„gmoa†hg€Nz̓200 mg/kg̔Jɼ ɺÉ2ƅŒ-ijǎǜ' ̓ ̓ ̝ ̔ ˅ ʸ ȵ ɗ 3  ¼ Ò Ʀ  C 7 ɳ ˖ ɷ ̎ 3 Ò Ʀ

Űʖ2Ų -̗˅ʸȵɗ3¼ÒƦC7ɳ˖ɷ̎3ÒƦJʏ*'
˅ʸȵɗ3¼ÒƦ̣̈ːˎãJʠˡ!F'?3ƁʐŪ3ãȂ2-̂˖˅ʸȵɗ J˻Ï̗ȵɗ2ɝɍJ' %3ṺːÉɺ:ĕØǻJá̗Éɺĕ3ĤäC 7̈ːD3Ǡ3ˆEÏJʛĻ' ʛĻɕ‘Ū̗ȵɗ2'ɝɍJɘɓ̗ D2ȦȷÝÐJȏ-ȵɗJÒƦ̗8''7Éɺĕ3ĤäC7Ǡ3ˆEÏJʛ Ļ' ãȂ3ijǎǚŪ̗ɫȦʜÚJʏȵɗ3ÒƦJȰʧ'
ɳ˖ɷ̎3ÒƦ̣Ʉ̞ɳNj3¦ɧ.ɷ̎ÒƦJʏ*' ɷNjJ˲ë-ɷ̎J˻Ï̗

10 ɷ̎JÒƦ'

̓ ̓ ̞ ̔ ̈ ː ˎ ã 3 ɫ Ȧ ȝ ʛ Ļ

ǟɈ:w€Ob‚„Ri~†‚JƎÅ̗%3Ri~†‚:˜Ŏăÿč̓Rodent Ventilator Model 683̣Harvard Bioscience, Boston, ɋĔ̔Jƒɞ' ˜Ŏăÿč 3ƒɞŪ̗¼3ɳ̍C7ɬ̍˩J̍ÒEˠ.Ò˨!F/2CEɳ̍JÒ˲' ɳ̍Ò˲Ū̗ůʀDǔ˴ɿ3˩2ɳ˖̈ːʛĻ.F/JȰʧ' ȰʧŪ̗ ̈ːÉɺ:ĕØǻJáF/.̈ːïɥJŹʹˎã3ǑŝJʛĻ!F//@2̗ f\aR{Jȏ'ãȒ3ʠˡJʏ*'
̓ ̟ ̔ R s Z M [ „ Ż ñ ŵ ȵ ɗ ȯ Ģ  c g 3 ª ʔ
RsZM[„JƧȍĮƵ3cg2ƅŒ!F/ Capsaicin ŻñŵȵɗȯĢG' cgJªʔ!F/.F̓Tsuda et al., 2000; Yamashita et al., 2008̔ % .̗RsZM[„̓10% Oal†̖10% Tween80 JþK(ȍȋ̈ĝǠ2Ƕʜ̔ 50mg/kg JȍŪ 2 ƫ̒3ƧȍĮcg2ȟŠƅŒ' RsZM[„Żñŵȵɗ3ȯ Ģ3ſý4̗89 ˋ̒Ư2 0.01%RsZM[„ǶǭJǽȦ'/3ȚʙîŲ2CE Ôĵ' !1I)ȦJÙɮF4Ūɮ.ƜFãªJȱ'cgJRsZM[„ ŻñŵȵɗȯĢG1*'¶¨̗ǿîŲ3cgJRsZM[„Żñŵȵɗȯ ĢG'¶¨.F/Ôĵ' ̓ ̠ ̔ ̈ ː ƙ Ï ǒ ƹ 2   F Ɇ ï ɥ î Ų 3 dz ĵ ̓in vitro Ķ̌̔ ̓ ̠ ̚ ̔ ǒ ƹ 3 ª ʔ
ãȂJM`q„.̐˘Ū̗ɹŠãɶÒ˨2CEƟʎǜ̗˅ʸȵɗJ³Ɗ 'Ȅż.ɏ1.0 cm 3˥3ɳ˖̈ːJƙÏ' ƙÏ'ɳ˖̈ː4̗ķDz3U‚ r]ǭŽ2!5Aǫǹ̗Ķ̌2­!F=.DŽ̋ǭŽ2-³İ'

̓ ̓ ̠ ̛ ̔ ï ɥ î Ų 3 ʠ ˡ
Ē̛2ȱ!C2̗̈ːƙÏǒƹƨJDŽ̋ǭ̓35 ̔.Ǵ'-F 10 mL Q S„m] 2ǫǹ' DŽ̋ǭ24̗95% O2̖5% CO2ǯùS]J­ɚ' ̈ ːǒƹ3ɂJɝɍ.ɘɓ' ‡ƨ4̗ɝɍ2CEQS„m]ġ2ēĵ̗@ ‡ƨ3ɂ4ɅŃŵg„]f~†Z†̓T7-8-240ORIENTECƾ—ƫƹ̔2 ƒɞ' ɅŃŵg„]f~†Z†DŬDG'˺ǟ´ö4L„s̓AC STRAIN AMPLIFIER AS1202̣NEC̗ƾ—̗ƫƹ̔Jš-ĠŖ̗Power Lab̓AD Instruments̔.ɤʸƨü3ïɥˎãJʠˡ' %G&G3ɖɦ24ÓƵʲʈ 1.0 g Já̗ł1/@ 30 Ñ˩ɧ-̗îŲijĵä'3)2̗Ķ̌2­' ̓ ̠ ̜ ̔ ˺ ǟ Ø ǻ ƨ ǣ
˅ʸȵɗØǻ4̗õ¼˅ʸȵɗƸɂJíǍÿÅ˺Ǎ.ÿŞ̗̈ːǒƹ/Ç2Q S„m]2ǫ'Ȅż.ʏ*' ˅ʸȵɗØǻ4˺ǍJ˺ǟØǻʒɧ̓Model SEN-3201̣ƫƹÃ˺̗ƾ—̗ƫƹ̔2+1̗˅ʸȵɗ2˺ǟØǻJá-ʏ*' ˅ʸȵɗ2Œ'˺ǟØǻ4̗ç‡ȪťǤØǻ3Ĝù4ØǻƊɞƯ˩10500 µȸ̗ Øǻ˺ĕ180 V /̗̚Ñ˩˴.á' ̄ďȪťǤØǻ3Ĝù4̗ØǻƊɞƯ ˩100 µȸ̗Øǻ˺ĕ80 V /̗120 Hz 3̄ś. 5 ȸ˩̗5 Ñ˩˴.á' ̓ ̠ ̝ ̔ ʌ Ȃ 3 ˓ ȏ ǣ
D-dvU€„̗LNAME 4ʊȔǠ2̗RsZM[„4Oal†2̗L-732,138 4˙˛Ob2%G&GǶʜ̗Ƴɕȝ2«ȏ!FǼś35001000 ·3]gcU Ƕǭ/' ʌȂ̈ːǒƹ2ŒFâǀJʬ;F'?̗]gcUǶǭJQS„ m]É2˓ȏ' ɘǀ2ʑʠG'ʌȂǼś4̗QS„m]É2FƳɕǼ ś.F Ƕĭ3˓ȏ4̗ǒƹ3ïɥǧŵ2ŧ̀JŒ1*'

12
̓ ̓ ̡ ̔ ɛ ʞ Î ȋ
ƹȭȽ.ŬDG'Ƣ¹f†a4̗ŗė¹ǒǵºŐ̓standard deviatioṇSD̔. ʑȱ' ƴźŐnjĵ4̗‡Á˗ɧÑơÑƿJȏ-njĵ'Ū̗Dunnet’s Ħ˝Ǟ ʼ2CEʜƿ' P ̤ 0.05 JɛʞIJȝ2ƴź/Ôĵ'

Ē Ē ̚
In vivo ̈ːˎã3dzĵĶ̌Ɏ ̂˖̈ːC7ɼ˖̈ːJ˻Ï̗w€Ob‚„ʔRi~†‚JƎÅ' ̂˖̈ː:3R i~†‚24̗ȍȋ̈ĝǠ.Ǵ''[€X„b~†rJƒɞ̗D2̗Dzȍȋ̈ĝǠ .Ǵ''x€QcgvgJƒɞ' ɼ˖̈ː:3Ri~†‚24ˆƨǧDžJȏ-Ñʼn #'[€X„b~†rJƒɞ' Ñʼn#'[€X„b~†r3Ʀɂ3‡ƨJx€Qcg vg3Ⱦǟó/ú ̏/1FC2ēĵ' ƦɂȡŠ2qP†]g„]f~†Z†2 ēĵ's]bcUĹčJɧ̗̈ːïɥˎã2C*-ȹˆG'ȍȋ̈ĝǠ3ďï̗%3 Ĺ˟JƓˆ˟/-dzĵ' œƨ3b~†r4̗ĕg„]f~†Z†Jƒɞ̗̈ːïɥ ˎã2C*-țȍ!FÉɺĕ3ĤäJʠˡ' ̈ːïɥˎãJțȊ#F'?̗x€Qcgvg3ǭ˾J‰Ƭ#F/.Éɺ:/ĕØ ǻJá' Øǻ3ţ4x€Qcgvg3ǭ˾3‰Ƭ¹2ĽŲ!FǠĕ (mmHg) /-ȱ'

14 Ē Ē ̛
ƙ Ï ̈ ː ǒ ƹ 2   F ǔ ɐ Ɇ ï ɥ î Ų 3 dz ĵ Ķ ̌ Ɏ ̈ːƙÏǒƹ4̗DŽ̋ǭ̓35 95% O2̖5% CO2ǯùS].ˇǟ̔JǴ'-F10 mL QS„m] 2ǫǹ' ̈ːǒƹ3ɂJɘɓ'ɝɍ.̗‡ɂ4QS„m]ġ2ēĵ̗ ‡ƨ4ɅŃŵg„]f~†Z†2ƒɞ' ɅŃŵg„]f~†Z†DŬDG'˺ǟ´ öJL„sJš-ĠŖ̗Power Lab .ɤʸƨü3ïɥˎãJʠˡ' ˅ʸȵɗJ˺ǟØ ǻ' ='̗ʌȂ4QS„m]É2ƅŒ'

Ʉ

Ʉ̚Ɂ

Ƨʘ

in vivo Ķ̌ɎJȏ'cg̈ːʍãˎã3ʜƿ

ɡ
ʝ

Ĉ  ã Ȃ 3 ̈ ː Ɇ ň 4 ̗ ŗ Ƿ Ɇ (  . 1  ̗ ǔ ɐ Ɇ . ǐ ſ  G F ˖ ¦   F ̓Neuhuber et al., 2006; Wörl and Neuhuber, 2005̔ ŗǷɆ̈ː3ˎã4̗ŁɻA ħ ɻ /  * ' œ 3 Ǭ ä Ɉ 3 ˎ ã / ú Ǒ 2 ̗ É Ė ȵ ɗ Ɏ 2 C * - × ŭ  G -  F ̓Furness, 2006; Clouse and Diamant, 2006̔ ‡ƨ̗ǔɐɆ̈ː3ˎã4̗Ŝ̎J š'˅ʸȵɗ2CFîľ2C*-ʬɉG-E̗ÉĖȵɗɎ2CF×ŭ4Ƴ˃= .</K0ƭD21*-1*'̓Andrew, 1956; Clouse and Diamant, 2006; Cunningham and Sawchenko, 1990; Goyal and Chaudhury, 2008; Jean, 2001; Lu and Bieger, 1998; Neuhuber et al., 2006̔ ˃Ř̗cg10+3ãȂ3ƙÏ ̈ːǒƹJȏ'ȭȽ2CE̗ÉĖȵɗɎ̈ːǔɐɆ3ˎã3×ŭ2˪Œ!F/ ƋƙG4 ?' %3ȭȽ/4̗ƙÏ̈ːǒƹ3ǔɐɆJ˅ʸȵɗ:3˺ǟØǻ 2CEïɥ#̗%:RsZM[„Apu€„/*'‡ǗŻʙȵɗ3ØǻʌJ˓ ȏ!F/@3.F̓Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2006; Shiina et al., 2012̔ GD3ʌÜ3˓ȏ2C*-ïɥî Ų4Ƅ×G̗D2̗3Ƅ×4aTTi„ñŨ˯ĸʌA‡˛äȿɒ̓NO̔ùſ ˚ɒ˯ĸʌ3İĖŠ.4ǰš'/D̗̈ːǔɐɆ3ˎã×ŭ24̗RsZM[ „Żñŵȵɗ/Ƅ×ŵÉĖȵɗDǐſGFŅƀîľɗʺ˪Œ-F/ƭ D/1*-F̓Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2006; Shiina et al., 2012̔ 3Ƅ×4̗ÉĖȵɗDƟÏG' NO ˅ʸˎãȵɗ2ªȏ̗L_bX€„ƟÏJƄ×!F/2CEțȊ!F@3/

16

ɪDG-F̓Izumi et al., 2003; Shiina et al., 2006̔ 3×ŭ3›ɖ>4̗ťż IJȝȭȽ.ƋƙG-'ÉĖȵɗ/˅ʸȵɗ3 co-innervation /‡ʃ-F ̓Neuhuber et al., 2006; Wörl and Neuhuber, 2005̔ G=.2ʜƭG-FƄ× ŵ3ȵɗɗʺJĒ̜2=/?'

RsZM[„Żñŵȵɗ4̗ȂȋȝäIJȝ°ĸØǻJñĹ-ǧŵä!F̓Holzer, 1988; Holzer, 2004; Geppetti and Trevisani, 2004; Sasamura and Kuraishi, 1999; Szallasi and Blumberg, 1999; Szolcsanyi and Bartho, 2001; Tominaga and Tominaga, 2005̔3.̗̈ːɈɺÉ3ŷěJñĹ-˅ʸȵɗ2CFˎã×ŭJʬƣ !F/Ÿĵ.F 1D̗̈ːǔɐɆˎã2Ľ-̗RsZM[„Żñ ŵȵɗďʺ03C1ŨÞJǀ'!3̗Ʒ(2ƭD21*-1 ƙÏǒƹ Jȏ'Ķ̌24Ǒ1ÖǽF@33̗3ȵɗďʺ2CFʬɉǖǐJCEʥɔ2 ʜƿ!F/24˰ȓF ̈ː3ʍãˎã4Žǁ2CF×ŭ3Á2ʹF3.̗R sZM[„Żñŵȵɗďʺ3ȍȋȝ1ǖɴJʜƿ!F'?24̗ŽǁȵɗɎ/3ƒɞ FȄż3Ķ̌Ɏ̗!1I)̗ʍãˎãĶ̌ȝ2ʨț.Fin vivo Ķ̌Ɏʖǡ GF
G=.2@̗̈ːǖɴJʤ¯!F'?3in vivo Ķ̌Ɏ4+ěĀG-' ¬5̗̈ːÉɺ.m†„J¥Ň#-Éɺ¼DĕØǻJáF/.ʍãˎã Jʨț!FĶ̌̓Lu and Bieger, 1998̔AŻʙȵɗ3îŲJ˺ǟȍȋIJȝ2ʠˡ!F Ķ̌̓Sengupta, 2001̗̔Żĕ_„Z†JʡɧʍãƯ3Éĕ3ĤäJ̈ː3H H1˖¦.ʠˡ!FĶ̌̓Lu and Bieger, 1998; Sang and Goyal, 2001̔ʏIG- F GD3Ķ̌2-4̗m†„AŻĕ_„Z†Jēĵ-F'?̗ȂʶJ ˆF/ʍãǖɴJǘȰ2ʤ¯-F0̗ÔƦ˽ŕ2˹ %3Ž.̗ MjJȏ'ʄĂǮĶ̌ʏIG-F̓Satchell, 1984̔ 3Ķ̌.4̗̐˘Š 3Mj3̈ːɂJɘɓ̗ÉɺJǠ.Ǵ''Ȅż̗!1I)˧ˣɎ.̗˅ʸŻʙ ȵɗ3ǧãJʠˡ!F/@3.F ƹȭȽ.4̗3Ķ̌ɎJƞĤ̗cg 2-̈ːɂJ˨ƟɎ2!F/.̗ʍãˎã2C*-ȍ Fǭ¨3ƓˆÄ̗

ːÉĕ3ĤäJʠˡ!F/3.FĶ̌JȰɀ.1/̗ɪF2ʂ*'
ȍ¨É2-̗îľJš'̈ːˎãJŞʹ!Øǻ/-4̗Ć̃ˎãD 3ØǻC7̈ːÉɺ3ÉĹȂ2CF¥ŇØǻDGF %.̗Žǁ/3ȵɗ ˊəJɟƊ'̐˘Š3cg̈ː2-ǭ¨JǨÅ#̗%G2CFĕß̈ː Éɺ2¥ŇØǻJŒ̗̈ːïɥˎãJʨț!FĶ̌ɎJǐŸ' ='̗ȂʶJȹ ˆ!Fʍãˎã3ɴßJʤ¯!F24Ķ˵2ȹˆ!F/3.'Ȃʶ3˟̗!1I )Ɠˆ˟Jdzĵ!F/ùȋȝ.F(Bogeski et al., 2005; Shimizu et al., 2006) %3'?̗ʍãˎãJʤ¯!F'?3n{†a†/-̗Éɺĕ3ĤäJʠˡ!F (.1̗Ɠˆ˟Jdzĵ!F/@ų̃2ɧ'
ž‰3ɱưJʻ=-̗ƹɁ.4̗ŽǁȵɗɎ/3ˊəJɟƊ'Ȅż.̈ːˎã Jʤ¯!F'?̗̐˘Š3cg2-̈ːʍãˎãJʠˡ.Fin vivo Ķ̌ɎJ Ȱɀ̗̈ːʍãˎã3ʤ¯Ɏ/-˓Ť0Jnjʟ!F/JȠȝ/'

18 Ē ̜
̈ ː ǔ ɐ Ɇ ˎ ã 2 Ľ ! F Ņ ƀ î ľ ɗ ʺ 2 C F × ŭ
3Ē4̗̈ːǔɐɆˎãJ×ŭ!FŅƀȵɗďʺJǓŝȝ2ȱ'@3.F 3ȵɗď ʺ4̗ƙÏ̈ːǒƹJȏ'in vitro Ķ̌Ɏ2C*-ƭD2G' RsZM[„Żñŵȵɗ ǧŵä!F/̗%DaTTi„ƟÏG̗aTTi„NO ªãŵÉĖȵɗJØǻ! F D2̗ÉĖȵɗDƟÏG'NO ˅ʸȵɗƸɂ2ªȏ-L_bX€„ƟÏJƄ ×-̗̈ːǔɐɆïɥJƄ×!F

ɘ

ɘ
ǀ

̓ ̚ ̔ ̈ ː É ɺ á ĕ Ø ǻ 2 C * - Ź ʹ  G F ʍ ã ˎ ã
̈ː̂˖2ƒɞ'x€Qcgvg3̏JĤä#F/2CË̗ːÉɺ2 FĕØǻ3ţJʬɉ' ĕØǻJŒ-1t†]3Ƽ Š̓0 mmHg̔. 4̗ăÿ3aMy„V/ĴÆ2úʬ'I"1Éĕ3ĤäʠˡG'̓Ē̝̔ x €QcgvgJ‰Ƭ#̗̈ːÉɺ2ĕØǻJŒF/̗N‚a„̐˘Š3Ƽ . 4̗F‡ĵž‰3Øǻţś̓4 mmHg̔2CË̗ːÉĕ3ħ1ĤäŞʹ G'̓Ē̝̔ ='̗Éĕ3ħ1Ĥä/úƯ2ǭ¨3ˆEÏ@ʧ?DG'̓Ē̝̔ ˜ŎăÿŠ.˨ɳ'Ȅż.̈ːˎãJɫȦȝ2ʛĻ'/H̗ʍãˎã3ȃŮ. Fóɺ¼Dɰ2üïɥʽȰʧG'̓Ē̞̔ 3/D̗̈ːÉɺ:3 ĕØǻ2CEŞʹGFÉĕ3ħ1Ĥä/%G2¤ǭ¨3ˆEÏ4̗̈ː ʍãˎã2CF@3.F/ɪDG'
‡ƨ̗Way„/-Uƒƒ†]3ǯù̐˘Š̓n = 4̗̔='4u„gmoa† ̐˘Š̓n = 4̔.4̗ƶ¨2- 8 mmHg =.ĕØǻƼ J‰-@̗ʍãˎ ãŹʹG1*'̓ĒʑȤȖ̔ ̓ ̛ ̔ ˅ ʸ ȵ ɗ Ò Ʀ  ʍ ã ˎ ã 2 Œ  F ŧ ̀
̈ːÉɺáĕØǻ2C*-ŹʹG'̈ː3ˎã̗˅ʸ-˅ʸȵɗîľ2CEŞ ʹG-F̈ːʍãˎã.F/JȰʧ!F'?̗˅ʸȵɗÒƦJ' ǿÎ ɧ3Ȅż.8 mmHg 3ÉɺĕØǻJŒ'/H̗ʍãˎãŞʹG̗úƯ2 ʎĕ3‰Ƭʹ*'̓Ē̟̔ ʍãˎãŞʹGF/JȰʧ'Ū̗ɞ-ŏ¼3˅ʸȵɗJÒƦ̗8 mmHg 3ÉɺĕØǻJŒ'/H̗ʎĕ3‰Ƭ4ʠˡ GF@33̗ʍãˎã4ŞʹG1*'̓Ē̟̔ D2¼3˅ʸȵɗJÒ Ʀ!F/.̗ʍãˎã3țȊC7ʎĕ3‰ƬǬĨ'̓Ē̟̔ Ķ̌4̜¬ʏI G̗%3Æ-3¶¨2-úǑ3ɘǀŬDG'

20 ̓ ̓ ̜ ̔ ̈ ː É ɺ á ĕ Ø ǻ 3 ̈ ː ʍ ã ˎ ã : 3 â ǀ
Ǘ2̗ĕØǻ3ţśJĤä#'/3̗̈ːʍãˎã2CFÉɺĕ3Ĥä̗Ɠˆ ˟̗ʎĕ3ĤäJʠˡ' ƶ¨2-̗̈ːÉ22 mmHg 3ĕØǻJŒ-@ ʍã4ŞʹG"̗4 mmHg :/ØǻJţ?F/.̗ʍãˎãŞʹG '̓Ē̠̔ ĕØǻJ4 mmHg D 8 mmHg :/Ġţ#'/H̗ʍãˎã3ʹ F̄ś4Ĥä#"̓Ē̡̥̗̔ç¦Ư˩Ť'E3Ɠˆ˟Ġá'̓Ē̡̦̔ D2̗ Øǻ3ţś2C*-‡ď'E3ʍãˎã03C2Ĥä!FJnjʟ!F'?̗ ̈ːÉĕ3Ĥä˟̗ƊɞƯ˩̗ƲɢŠ˾ȼJdzĵ…Ǟʼ'̓Ē̢̔ Øǻ3ţśJ4 mmHg D 8 mmHg :/ţ!F/.̗Éĕ3Ĥä˟̗ƲɢŠ˾ȼ4Ġá'‡ƨ ̓Ē̢̧̥̗̗̔ƊɞƯ˩4Ĥä1*'̓Ē̢̦̔ ŗėʎĕ4Øǻţś3Ġá2 ū*-̗‰Ƭ'̓Ē̡̧̠̗̔

Ē

Ē ̝
̈ ː É ɺ : 3 á ĕ Ø ǻ 2 C F ʍ ã ˎ ã 3 ʨ ț

Ē4̗̐˘ŠcgJĒ̛2ȱ'C1Ķ̌Ɏ2_cg̗dzĵ'in vivo ̈ːˎãJȱ -F ‰D̗̈ːÉĕ̓mmHg̗̔Ɠˆ˟̓mL̗̔ʎĕ̓mmHg̔3ʑȝ1g‚†]. F ̈ːÉɺ:3áĕØǻ4̗0 D 1 mmHg "+‰Ƭ#̗Ƴħ 4 mmHg =.Œ'

22 Ē Ē ̞
In vivo ̈ːˎã3ɫȦ2CFʛĻ¾
3Ē4̗̐˘Šcg3ɳ˖J˨̗̈ːJ˻Ï#-̗̈ːÉɺ:áĕØǻ4 mmHg J á'˵2ƚŧ'Ëȥ.F ønkŏ‰3Ƣ¹4Ư˩ɗˏJȱ-F Ȩé4̗̈ː2 țȍ'ïɥʽ3¦ɧJȱ-F

Ē Ē ̟
˅ ʸ ȵ ɗ 3 Ò Ʀ  ̈ ː ʍ ã ˎ ã 2 Œ  F ŧ ̀
Ē4̗ǿÎɧ̗ŏ¼˅ʸȵɗÒ˲Ū̗¼˅ʸȵɗÒ˲Ū2̗%G&G̈ːÉɺ:8 mmHg 3áĕØǻJŒ'˵3̈ːÉĕ̓mmHg̗̔Ɠˆ˟̓mL̗̔ʎĕ̓mmHg̔3g‚†].F ƳŠǛ4̈ːÉĕ3̥̗̦˖Jƈħ'@3.F Ē3g‚†]4Æ-ú‡¶¨DʠˡG '@3.F

24 Ē Ē ̠
̈ ː É ɺ : 3 á ĕ Ø ǻ Ƽ   3 Ġ á 2 ¤  ̈ ː ʍ ã ˎ ã 3 Ĥ ä


Ē4̗2̗4̗8 mmHg 3ĕØǻJá'˵3̗in vivo ̈ːˎãJȱ-F ‰D̗̈ː Éĕ̓mmHg̗̔Ɠˆ˟̓mL̗̔ʎĕ̓mmHg̔C7̈ːÉĕ3ʑȝ1g‚†].F = 'ƳŠǛ4̈ːÉĕ3̥̗̦̗c J%G&Gƈħ'Ē.F

Ē ̡
̈ ː É ɺ : 3 á ĕ Ø ǻ Ƽ    ̈ ː ʍ ã ˎ ã 3 ̄ ś ̗ Ɠ ˆ ˟ ̗ ŗ ė ʎ ĕ : Œ  F ŧ ̀
Ē4̗2̗4̗8 mmHg 3ĕØǻJá'˵2dzĵG' in vivo ̈ːˎã3n{†a†JV q2-=/?'@3.F Ēa 4ˎã̄ś̓ď̘ȸ̗̔Ē b 4Ɠˆ˟̓µL̘ȸ̗̔Ē c 4 ŗėʎĕ̓mmHg̔.F øVq3Ƣ¹4̗ŗė¹SD .ȱ-F(n = 6) ̕4P < 0.05 .ɨ2ƴźŐF/Jʑ-F

26 Ē Ē ̢
̈ ː É ɺ : 3 á ĕ Ø ǻ Ƽ   3 ʍ ã ˎ ã 2 C F É ɺ ĕ 3 Ĥ ä ˟  C 7 ‡ ď 3 ʍ ã 3 Ɗ ɞ Ư ˩ : 3 ŧ ̀
‰Ǜ4̗8 mmHg 3ĕØǻJá'˵2ʠˡG'̈ːÉĕĤä3ʑȝ1g‚†].F a 4̈ːʍãˎã2CFĕĤä3ĠŖ̓Éĕ3Ĥä˟̗̔b 4̈ːʍãˎã2CFĕĤä3Ɗɞ Ư˩̗c 4ƲɢŠ˾ȼJȱ-F d 4ʍãˎã3/2ʠˡG'lM^.F Ē4̗2̗ 4̗8 mmHg 3ĕØǻJá'˵2dzĵG' in vivo ̈ːʍãˎã3n{†a†JVq2 -=/?'@3.F Ēa 4ʍãˎã2CFÉĕ3Ĥä˟̓mmHg̗̔Ē b 4‡ď3ʍã 3ƊɞƯ˩̓ȸ̔Jȱ-F øVq3Ƣ¹4̗ŗė¹SD .ȱ-F(n = 6) ̕4P < 0.05 .ɨ2ƴźŐF/Jʑ-F

ɪ

ɪ
Ļ

ƹɁ.4̗ÉɺáĕØǻ2C*-̈ːʍãˎãJŹʹ#Fin vivo Ķ̌Ɏ3ȰɀJ ʏ*' ̈ː3Éɺ2ĕØǻJáF/2C*-̗ɰ¼:ü*-Ǥì!Fïɥʽ țȍ̗̈ːÉɺĕ3‡ˏŵ3‰Ƭ2úʬ-̗ÉɺǭˆEÏG' 3C1̈ ː3îŲ4̗ĕØǻ1.4ʛĻG1/D̗̈ːÉɺ:3ĕØǻ*-4 ?-țȊ!F@3.F/F D2̗˅ʸȵɗÒƦ2CE̗GD̈ːÉɺĕ3 Ĥä@Éɺǭ3ˆEÏ@ʹD11*' G4̗̈ːʍãˎã˅ʸ˅ʸȵɗ îľ2C*-×ŭG-F/Ǐų/‡ʃ'Ȋʱ.F ž‰3/D̗ƹɁ .4̗in vivo .ǔɐɆ̈ː2FʍãˎãJʨț!F'?3Ƨ'1Ķ̌Ɏ3Ȱɀ2 ſà'/F 3Ķ̌Ɏ.4̗ÉɺĕĤä/Ɠˆ˟/̛+3n{†a†J dzĵ!F/.̗̈ːʍãJĵ˟ȝ2ʤ¯!F/ôɴ/1F

̈ːʍãˎã24̛+3ˎãǑŝF/ȩDG-F̓Clouse and Diamant, 2006̔ 6/+4̗‡Ǘʍã/ă5GF@3.̗ϊ2C*-ʨțGFˎã.F @6/+4̗”Ǘʍã/ă5GF@3.̗̈ːÉɺ3̈ȂD3¥ŇØǻ2C*-̈ ː¨˖.ŞʹGFʍãǤ3/.F ƹɁ.ȰʧG'ʍã4”Ǘʍã2Ñ̇ GF@3.F 1$1D̗.>DGFîŲ4̗ϊ4#"2̗̈ːÉɺ:3ĕ Øǻ2C*-̈ː¨˖.ȍ F@3.FD.F ”ǗʍãJĶ̌ȝ2¡ź3aM y„V.ʨț!F'?2̗̈ːÉ2ʡɧ'm†„J¥Ň#FƨǣȏDG- '̓Lu and Bieger, 1998̗̔ƹȭȽ.Ȱɀ'ƨǣ4ĕĤä(.1Ɠˆ˟Jú Ư2dzĵ.FÀ¦ŵJƊ*-F

ϊŽǁ4̗ɸř3Ŝ̎ıƻLJ2İĖ-E̗˅ʸ˅ʸȵɗîľJš-̈ːǔ ɐɆ3ʍãJ×ŭ-F̓Clouse and Diamant, 2006; Bieger and Neuhuber 2006; Lu and Bieger, 1998̔ Ŝ̎ıƻLJ24̗NMDA ñŨA GABA ñŨİĖ- F  G D 3 ñ Ĺ ¨ 4 ̈ ː ˎ ã 3 ɛ ù 2 ˪ Œ  -  F ̓Broussard et al., 1996; Broussard et al., 1994̔ Ķ˵̗GD3ñŨ3LYi]gAL„aYi]gJÎɧ

28

!F/̗̈ː3ˎãǧŵƄ×GF̓Hashimo and Bieger, 1989; Wang and Bieger, 1991̔ 3/4̗Way„̓NMDA ñŨL„aYi]g̔Au„gmoa† ̓GABA ñŨLYi]g̔2CF̐˘Š.4̈ːʍã4țȊ1*'//‡ ʃ-F ̐˘ʌ3˔Ƈ4̗in vivo ̈ːˎã3Ķ̌Ɏ2-˝ʖ.F
Ȱɀ'cg̈ːˎãĶ̌Ɏ.4̗C%4 mmHg 3¥ŇØǻ2CE̗ʍãˎã ʨțG' MjA||cg3̈ːJȏ'ȭȽ.̗̈ːÉɺ2ǭ¨JǴ'-ĕØǻJáF/̗̝6 mmHg 3ĕØǻ2îŲ!F§ˬ¹3˅ʸŻʙȵɗİĖ -F/ƭD21*-F̓Satchell, 1984; Yu et al., 2005̔ 3Żʙȵɗɨ ʍãˎã3țȊ2ĺŒ-F/ɪDG̗3ȩʗ/ƹȭȽ.3ʍãʨț3ĕØ ǻƼ /‡ʃ-F ='̗̈ːÉɺ2ĕØǻJŒF/.̗ʎĕ3‰Ƭʹ *' G4̗̈ːÉɺ3¥ŇØǻ4˅ʸŻʙȵɗ.ñĹG-Žǁ:/£DG 'ɘǀ̗ɷ̎–Żȵɗ2CEʎĕ‰Ƭ!F̓Loomis et al., 1997̔/2CF@3( H Ķ˵2̗¼3˅ʸȵɗJÒƦ!F/̗ʎĕ3‰Ƭ4ʧ?DG11*'  3ʎĕ3‰Ƭ4̗ĕØǻ3Ġá2Ų -îŲħ1F/D̗3Ķ̌Ɏ.ʏ *'2̗4̗8 mmHg 3ĕØǻ4ȗ1Fħ3Øǻ/-˅ʸŻʙȵɗ̗%-Žǁ :/£ˑG̗ʧʰG-F/ɪDGF
ʄĂǮ/2̗̈ː3ʍãˎã4ȁ¼3˅ʸȵɗJÒƦ!F/2CEʨțG 11*' ʎĕ3‰Ƭȁ¼3>3ÒƦ.4ǬĨ1/D̗ƹȭȽ.ȏ' Ɓƃ4̗îĽ¼3˅ʸȵɗ2˶ĸJŒF/1ȁ¼3>JÒƦ-F/I F ¼3˅ʸȵɗ»ŕ.1/̗˅ʸ˅ʸȵɗîľ2CFʍãˎãʨțG 1//21F̗%3ȋȐ4‹ƭ.F ̚+3ôɴŵ/-̗ȁ¼3˅ʸȵ ɗJ‰ʏ!FŻʙŷěŽǁ.ɛùG'Ū̗îĽ¼3˅ʸȵɗJŠʏ-̈ːǔɐɆ Jïɥ#FǑŝɪDGF 3C1ǑŝJŸĵ!G5̗ȁ¼JÒƦ!F/˅ʸ ˅ʸȵɗîľǬĨ!F/=ʪƭ.F ™Ū3njʟʫ̅.F/ʝF
Ȱɀ'in vivo ̈ːˎãĶ̌ɎJȏ-̗cg̈ːʍãˎã3ŵʶJʜƿ' ̈ːÉɺĕØǻJĠţ!F/̗ç¦Ư˩Ť'E3Ɠˆ˟Ġá'32Ľ̗ʍãˎ

ã3̄ś24Ĥä>DG1*' ‡ƨ̗ʍãˎã2CF̈ːÉĕ3Ĥä˟̗Ɗɞ Ư˩̗ƲɢŠ˾ȼJǞʼ'/H̗Éĕ3Ĥä˟̗ƲɢŠ˾ȼ4Øǻ3ţś2Ų -Ġá!F@33̗ƊɞƯ˩4Ĥä1*' 3/4̗Øǻ3Ġţ2C*-‡ ď'E3ʍã3ţĠ̗CEĦ3ÉĹȂJˆEÏ'/ʜ˜!F3ùȋȝ (H Éɺ:3ĕØǻ3ħ4̈ːÉɺ3Ȃʶ3˟JîƮ-F'?̗̈ː4 Ƙð'̈Ȃ3˟2Ų -̗ʍã3ďƢAˈJĠA!3.41̗‡ď3ʍã2C FˎƗɴßJĤä#F/ʬɉJʏ*-F/ɪDGF
ʍã3̄śĠá1*'/4̗ú C1ĕØǻ2C*-ʍãJʨț!FĶ ̌Ɏ2-̄śĠá!FŁɻ3ʍãˎã/4ȗ1FȊʱ.F 3‹‡ʃ4̗ ̈ː/Łɻ/3ǖɴȝ1˒JîƮ'@3.F@G1 ÉɺáĕØǻ3ħ 4ǬäɈÉɺ3Ȃʶ3˟JîƮ-F %3'?̗ĕØǻ3ţ2Ų 'ʍã ˎã3Ĥä4̗Éɺ3ȂʶJ03C2ȹˆ!F/ʍãǖɴ3ŵʶJCîƮ '@3(/F Łɻ3Ĝù̗ʍã3̄śJ‰F/4̗ēťȂJȯȮ̗F 4̗ƷǬäȂJʾˆ!F'?2Űʖ1/13.H ‡ƨ̗̈ː3ǖɴ4Ƙð '̈ȂJɰ=.ˎ9/!;-.F ̈ːÉɺ2ÉĹȂǸȔ!F/413.̗ ʍãîľJʨț!FĕØǻ4‡ˏȝ.F/Ħ %3'?̗̈ː2-ˊɞ 'ʍãˎãʹF/4ƫŕ3ϊˏȺ.4=G.F(H ̈ː24ʍã3̄ś J‰F›ɖ>41/ɪF/ĪŤ.F
ž‰3C2ƹɁ.4̗̈ː2FʍãˎãJʨț.Fin vivo Ķ̌ɎJȰɀ! F/2ſà' 3Ķ̌Ɏ4̗̈ːˎãǖɴ3ŵʶAɴßJʤ¯!F/2˓ -F/ɪDG̗ʍãˎãJ×ŭ!Fȵɗďʺ3ʜƿ2Öȏ.F@3/.F/ F

30

Ʉ

Ʉ̛Ɂ

̈ːʍãˎã2Ľ!FRsZM[„Żñŵȵɗ3Ɗ+

ʬɉȝ1ŨÞ

ɡ
ʝ

Ʉ̚Ɂ.4̗in vivo .̈ːˎãJʤ¯!FĶ̌ɎJȰɀ' 3Ķ̌Ɏ.4̗̈ ːÉɺ:3ĕØǻ2C*-ʍãˎãʨțG̗Éɺĕ3ĤäʠˡGF//@2̗ ÉɺǭˆEÏGF Éɺ:3ĕØǻ2C*-ȍ F̈ːˎã4̗Ƙð'̈Ȃ2C F̈ːġ:3¥ŇØǻ2C*-ʨțGFȍȋȝ1ʍãˎã/>1!/.̗̈ː ʍãˎã3ŵʶAɴßJʤ¯!F/ôɴ.F
G=.2̗RsZM[„3TRPV1 :3ªȏ2C*-ʄĩ'RsZM[„Żñŵ ‡ǗŻʙȵɗ4̗Ƅ×ŵ3ÉĖȵɗJš-˅ʸȵɗD3L_bX€„ƟÏJƄ ×̗ɘǀ/-̈ːˎãJƄ×!F/̈ːƙÏǒƹJȏ'Ķ̌2-ƭD /1*-F̓Ē̜; Izumi et al., 2003; Shiina et al., 2006̔ 1D̗G D3Ķ̌4ƙÏG'̈ːǒƹ2FĶ̌.E̗RsZM[„ŻñŵŻʙȵɗ C7ÉĖȵɗDǐſGFŅƀîľɗʺ3̈ːˎã3×ŭ2Fȍȋȝ1ŨÞ4 ƭD2G-1 @̗3RsZM[„Żñŵȵɗďʺ̗̈ːʍãˎã3 ×ŭ2ȍȋȝ2˪Œ!F3.G5̗RsZM[„ŻñŵȵɗȯĢcg2F̈ ːˎã4̗ǘŕcg3%G/©D3ǖɴȝ1ŐȗF4".F In vivo Ķ̌ ɎJȏF/.̗%3ŐȗJʜƿ!F/4ôɴ.H
%.ƹɁ.4̗RsZM[„ŻñŵȵɗȯĢcgC7ǿÎɧcg3̈ːˎ ã3ŵʶAɴßJǞʼ̗RsZM[„ŻñŵȵɗC7%G2C*-ʄĩGFÉ Ėȵɗ3̈ːˎã2Ľ!Fȍȋȝ1ŨÞJƭD2!F/Ƞȝ/'

ɘ

ɘ
ǀ

̓ ̚ ̔̈ ː É ɺ á ĕ Ø ǻ 2 C * - Ź ʹ  G F ʍ ã ˎ ã 2 Ľ ! F R s Z M [ „ Ż ñ ŵ Ż ʙ ȵ ɗ ȯ Ģ 3 ŧ ̀
RsZM[„Îɧ2CERsZM[„ŻñŵȵɗJȯĢ'cg/ǿÎɧcg 3̈ːʍãˎãJin vivo Ķ̌ɎJȏ-Ǟʼ' ̈ː2¥ŇØǻJŒ'/H̗ 0)D3̈ː2-@ʍãˎãʨțG'̓Ē̙̔̚ ǿÎɧcg.4̗4 mmHg CE@§ĕØǻ.ʍãʨțG'¶¨41*'̗RsZM[„Îɧcg. 42 mmHg 3ĕØǻ2C*-ʍãțȊ' ʍãˎã3̄ś2ɨ˩.Ő41 *'̓Ē̥̔̚̚ ‡ƨ̗ç¦Ư˩'E3Ɠˆ˟2+-4̗RsZM[„Żñŵȵ ɗJȯĢ'cg3ƨħ*'̓Ē̦̔̚̚ ̈ːÉɺáĕØǻ2C*-ȍ F ŗėʎĕ3‰Ƭ4̗ɨ˩.Ő41*'̓Ȩ̄̔̚̚ ̓ ̛ ̔ ̈ ː X „ s  M L „ ] 2 Ľ ! F R s Z M [ „ Î ɧ 3 ŧ ̀
RsZM[„Îɧ2CË̗ː¥ŇA!1*'0Jʤ¯J!F'?̗ ĕØǻJá'/3̈ːȡũ̓X„sML„]̔Jʞdz' X„sML„]4 ɨ˩.Ő1*'̓Ē̛̔̚ ̓ ̜ ̔ʍ ã ˎ 㠇 ď  ' E 3 ŵ ʶ 2 Ľ ! F R s Z M [ „ Ż ñ ŵ Ż ʙ ȵ ɗ ȯ Ģ 3 ŧ ̀
ʍãˎã‡ď'E3̈ːÉɺĕ3ĤäJǞʼ' ʍãˎã2CFÉĕ3Ĥä3 ǑŝJǞʼ'/H̗ǘŕcg̈ː.4ç‡3̏p†U3FĕĤäʠˡ G'32Ľ̗RsZM[„ŻñŵȵɗȯĢcg̈ː.4%3p†UǬĨ̗ʕ Ƣ3§p†U3FĕĤäʠˡG'̓Ē̜̥̔̚ ='̗RsZM[„Żñŵȵ ɗ3ȯĢ2CE̗ʍãˎã2CFÉɺĕĤä3ƍŖ4ǰł̗ÉɺĕĤä3ƊɞƯ˩ C7ƲɢŠ˾ȼ4Ġá'̓Ȩ̨̜̦̗̗̄̔̚

32 ̓ ̓ ̝ ̔ ̈ ː ʍ ã ˎ ã 3 ʨ ț 2 Ľ ! F ɷ ̎ Ò Ʀ 3 ŧ ̀
RsZM[„Żñŵȵɗ3ªȏƸljŵ2țȊ!F3̗%G/@Žǁȵɗ2®İ -țƖGF3Jʬ;F'?2̗3 ¬3ǿÎɧcg2-ɷ̎ÒƦJʏ*' ɷ̎JÒƦ'cg.4̗RsZM[„ŻñŵȵɗȯĢcg/ú C2̗2 mmHg 3Ǟʼȝ§ĕØǻ2C*-ʍãțȊ'̓Ē̝̔̚ 1D̗ç‡3 ̏p†U3FĕĤä4ĤID1*' %3œ3n{†a†@̗ǿÎɧcg /˒4ʧ?DG1*'

Ē

Ē ̚ ̙
ǿ Î ɧ  C 7 R s Z M [ „ Î ɧ  c g ̈ ː 2   F ʍ ã ˎ ã

Ē4ǿÎɧC7RsZM[„Îɧcg2̗̈ːÉɺ:8 mmHg 3áĕØǻJŒ'/ 2ʠˡG'̈ːˎãJȱ-F ‰D̗̈ːÉĕ̓mmHg̗̔Ɠˆ˟̓mL̗̔ʎĕ̓mmHg̔ 3ʑȝ1g‚†].F ='ƳŠǛ4̈ːÉĕ3̥̗̦J%G&Gƈħ'Ē.F

34 Ē Ē ̚ ̚
̈ ː ʍ ã ˎ ã 3 ̄ ś  Ɠ ˆ ˟  ŗ ė ʎ ĕ 2 Ľ ! F R s Z M [ „ Î ɧ 3 ŧ ̀
Ē4̗ǿÎɧC7RsZM[„Îɧcg2-̗2̗4̗8 mmHg 3ĕØǻJá'˵ 2dzĵG'in vivo ̈ːˎã3n{†a†JVq2-=/?'@3.F ȜRz ǿÎɧcg̗̑RzRsZM[„ÎɧcgJʑ-F Ē a 4ˎã̄ś̓ď̘ȸ̗̔ Ē̦4Ɠˆ˟̓µL̘ȸ̗̔Ȩ̄4ŗėʎĕ3‰Ƭ¹̓mmHg̔.F øVq3Ƣ¹4̗ŗ ė¹SD .ȱ-F̓ǿÎɧɨ̣n = 6̗RsZM[„Îɧɨ̣n = 5̔ ̕4P < 0.05 . ɨ2ƴźŐF/Jʑ-F

Ē Ē ̚ ̛
̈ ː á ĕ Ø ǻ Ư 3 ̈ ː ȡ ũ 2 Ľ ! F R s Z M [ „ Î ɧ 3 ŧ ̀
Ē4̗ǿÎɧC7RsZM[„Îɧcg2-̗0 ='4 8 mmHg 3ĕØǻJá' ˵2dzĵG'̈ːȡũJVq2-=/?'@3.F ȜRzǿÎɧcg̗̑R zRsZM[„ÎɧcgJʑ-F øVq3Ƣ¹4̗ŗė¹SD .ȱ-F̓ǿ Îɧɨ̣n = 3̗RsZM[„Îɧɨ̣n = 3̔

36 Ē ̚ ̜
̈ ː ʍ ã ˎ ã 2 C F É ɺ ĕ 3 Ĥ ä ˟  C 7 ʍ ã 3 Ɗ ɞ Ư ˩ : 3 R s Z M [ „ Î ɧ 3 ŧ ̀
Ēa 4̗ǿÎɧC7RsZM[„Îɧcg2-̗8 mmHg 3ĕØǻJá'˵2ʠ ˡG'̈ːÉĕĤä3ʑȝ1g‚†].F Ȩ̨̦̗̗̄4̗2̗4̗8 mmHg 3ĕØǻ Já'˵2dzĵG'in vivo ̈ːʍãˎã3n{†a†JVq2-=/?'@3. F Ēb 4ʍãˎã2CFÉĕ3Ĥä˟̓mmHg̗̔Ȩ̄4‡ď3ʍã3ƊɞƯ˩̓ȸ̗̔Ē ̨4ƲɢŠ˾ȼJȱ-F ȜRzǿÎɧcg̗̑RzRsZM[„ÎɧcgJ ʑ-F øVq3Ƣ¹4̗ŗė¹SD .ȱ-F̓ǿÎɧɨ̣n = 6̗RsZM[„Î ɧɨ̣n = 5̔ ̕4P < 0.05 .ɨ2ƴźŐF/Jʑ-F

Ē Ē ̚ ̝
̈ ː ʍ ã ˎ ã 3 ț ȍ 2 Ľ ! F ɷ ̎ Ò Ʀ 3 ŧ ̀ Ē4̗ǿÎɧC7ɷ̎ÒƦcgDdzĵ'in vivo ̈ːˎã2CFÉĕĤä̓mmHg̔ 3ʑȝ1g‚†].F ̈ːÉɺ:0̗2̗4 mmHg 3ĕØǻJá'/H̗ǿÎɧɨ. 44 mmHg 3ĕØǻ2C*-̈ːʍãˎãʨțG' ‡ƨ̗ɷ̎ÒƦɨ.4̗CE§ 2 mmHg 3ĕØǻ2C*-̈ːʍãˎãʨțG'

38

ɪ

ɪ
Ļ

ƹɁ.4̗RsZM[„JƧȍĮƵ2Îɧ-RsZM[„ŻñŵȵɗJȯĢ' cg/ǿÎɧcg3̈ːʍãˎãJin vivo Ķ̌ɎJȏ-Ǟʼ' ̈ː2¥Ň ØǻJŒ'/H̗ʍãțȊ!FˬØǻ24˒F@33̗RsZM[„Ż ñŵȵɗJȯĢ'cg3̈ː2-@ʍãˎã%3@34ʨțG' ˅ʸȵ ɗÒƦ2C*-ʍãîľĴÆ2ǬĨ!F/̓Ʉ̚Ɂ̔JɪF/̗RsZM[„˽ Żñŵ3˅ʸŻʙȵɗ2ʍã3ʨț2˪Œ!F/F RsZM[„Żñŵȵ ɗ4‡ʅȝ2̏ˬ¹Żʙȵɗ̗!1I)Ǟʼȝ̏Øǻ2Ų -îŲ!Fȵɗ2Ñ̇ GF̓Spencer et al., 2008; Yu et al., 2005̔ ƹȭȽ.á'ĕØǻ4˽°ĸØǻ ‚t.E̗§ˬ¹Żʙȵɗ4ǧŵä!F̗̏ˬ¹Żʙȵɗ4ǧŵä.1 ='̗̈ː2ÑŒ!F˅ʸŻʙȵɗ3ɕƸǐˉ4̗Intraganglionic laminar endings ̓IGLE̔2Ñ̇G̓Berthoud et al., 1997a; Phillips and Powley, 2000; Sengupta, 2000; Zagorodnyuk and Brookes, 2000̔3ǐˉJ@+ȵɗ4RsZM[„˽Żñ ŵ.F̓Berthoud et al., 1997b; Patterson et al., 2003̔ GD3/D@̗§ ˬ¹˅ʸŻʙȵɗĕØǻ2Ų -ʄĩ̗˅ʸȵɗîľJš-̈ːʍãˎãJʨ ț-F/ɪDGF ʝƕF/̗̏ˬ¹Żʙȵɗ.FRsZM[„Żñŵ ȵɗ4̗ʍãˎã3țȊʁ¨24ȡƒ˪Œ-1/Jȱĉ-F
ƹȭȽ31Ƞȝ4̗RsZM[„Żñŵȵɗ/ÉĖȵɗ2C*-ǐſGFŅƀ ȵɗďʺ̗̈ːʍãˎã3×ŭ2Ľ-03C1ŨÞJƊ*-F3ƭD2 !F/.F RsZM[„ŻñŵȵɗȯĢcg.4̗̈ːÉɺáĕØǻ2C* -ʨțG'ʍãˎã2CE̗˥ƊɞƯ˩J@*'ʕƢ§p†UJƊ+ÉɺĕĤ äʠˡG' 3/4̗ɛùG-1̈ːɆïɥʹE̗B*E/ 'ˈś3ʍãˎã2Ĥä'/ɪDGF 3ɘǀ4̗RsZM[„Żñŵȵɗďʺ ̗ʍãˎã3ɛù2ĺŒ-F/Jȱĉ-F 3ȵɗďʺF/.̗ ̈ːǔɐɆ3ɛùG'ïɥîŲʹE̗ɘǀ/-!5ÄːʍãˎãĶȊ.

̗Ƙð'̈Ȃ3âȈȝ1ȹˆʏIGF3@G1 RsZM[„Żñŵȵɗ 4̗̈ː2¥ŇØǻáI*'˵̗¶3̈ːǔɐɆ3ïɥ2-Ƅ×J̗ï ɥ2Ƴ˓1aMy„V.%3Ƅ×DʜƟ!F/.̗̈ːÆ˥2I'Fïɥʽ3ȹ ã̗+=EßţʍãˎãJŞʹ!Cǖɴ-F/ɪDGF ƹȭȽ4̗ ̈ːʍãˎã2FÉĖŵȵɗďʺ3ȍȋȝŨÞJʜƭ'ƳÓ3ȭȽ.F
RsZM[„ŻñŵȵɗȯĢcg2F@6/+3ʄĂǮȩʗ4̗ǘŕ cgCE@§ĕØǻ.ʍãˎãʨțG'/.F ĕØǻ2C*-ʨțG Fʍãˎã4̗˅ʸ˅ʸȵɗîľ2C*-×ŭG-F̓Andrew, 1956; Clouse and Diamant, 2006; Cunningham and Sawchenko, 1990; Goyal and Chaudhury, 2008; Jean, 2001; Lu and Bieger, 1998; Neuhuber et al., 2006̔ %3'?̗ˬ¹3 §Š4˅ʸŻʙȵɗ3Żñŵ2êĐFôɴŵ̏ RsZM[„Żñŵȵɗ ĕØǻ3˓ȏŪ2©D3Ƅ×ǖǐJǧŵä!F %GB2̗RsZM[„Żñŵ ȵɗ3ȯĢ2CE̗%3Ƅ×ǖǐ½"2̗ˬØǻ§Š'/6/+3Ÿʪ ɪDGF 1D̗ƹȭȽ.̈ː2á'ĕØǻ4̗̏ˬ¹Żʙȵɗ. FRsZM[„ŻñŵȵɗJǧŵä#F24§!F̓Spencer et al., 2008; Yu et al., 2005̔3.̗3ôɴŵ4§@G1 @6/+3Ÿʪ4̗RsZM[„ Żñŵȵɗ˅ʸȵɗ3ǖNJñĹč2Ɗɞȝ2ƄתȏJ@'D-F// .F 3ôɴŵ4̗RsZM[„ŻñŵȵɗʁțȝƊɞȝ2ǧŵäF/ ěĀ2C*-ƝƊGF̓Banik and Brennan, 2009; Rong et al., 2004̔ 3Ɗ ɞȝ1Ƅ×ĐĮ/-̗NO ɪDGF ÉĖŵ3 NO 4ǬäɈ3˅ʸŻʙȵɗ2Ľ -Ƅ×ŵȵɗʬɉĐĮ/-ǖɴ-F̓Page et al., 2009̔ “Ķ̗ƙÏǒƹ.ʜ ƿG'RsZM[„Żñŵȵɗďʺ3ǐſĐĮ36/+4̗NO ªãŵȵɗ.F ̓Shiina et al., 2013; Shiina et al., 2006̔ C*-̗ÉĖȵɗ2C*-ùſG' NO ˅ʸŻʙȵɗ3ǖNJØǻñĹǖǐJƄ×ȝ2×ŭ-Fôɴŵ̏ ='̗Ƨȍ ĮƵ3RsZM[„Îɧ2CE̗ɷ̎ɱLjȵɗɉ.3n-NOS ˳ŵȵɗɔɲƢ3ǰł ʹE̗ł1/@2 ˋ˩ɞ/ěĀG-F̓Masliukov et al., 2015̔ ƹȭ

40 Ƚ2-4ÄȘǂʆ102CFƸljŵ3n-NOS țȊ˟3njʟ4ʏ*-D"̗=' RsZM[„ÎɧŪ2NO ªãŵȵɗžĥ3ȵɗ¿ȝ2Ġá…ǰł!Fôɴŵ10 @™Ūnjʟ!;ʫ̅.F̗RsZM[„ŻñŵȵɗJȯĢ!F/.̈ːʍãˎ ãĤä'ʖĐ3‡+24NO 2CFʬɉǖǐ3ĤäƌDGF.H 1̗ RsZM[„ŻñŵȵɗJʹǽ/!FƄ×ŵ3ŅƀȵɗďʺŶŕȝ2ǖɴ-F ôɴŵ2+-4̗Ʉ̜Ɂ.Ķ̌f†aJÁ2ʭ F
̈ːʍãˎã4ŽǁȵɗɎJš'ˎã.E̗RsZM[„Żñŵȵɗ2CFʬ ɉ2-@Žǁ3˪ŒJɪŽ!;.F ̈ː/ŽǁJɘ9Żʙȵɗ24˅ʸȵ ɗ/ɷ̎ȵɗ3̛+E̗cg̈ː2FRsZM[„Żñŵ3Żʙȵɗ4 2ɷ̎2Ȑƽ'ĥƽȵɗ.F̓Berthoud et al., 1997b; Shiina et al., 2006̔/3 ěĀF ƹȭȽ2-@̗˅ʸȵɗ2C*-ŞʹGFʎĕ3‰ƬRs ZM[„Îɧ3ŧ̀Jñ1*'/D̗˅ʸŻʙȵɗ4RsZM[„˽Żñŵ .F/ɪDGF ž‰3/D̗RsZM[„Żñŵȵɗ2CFŽǁŵ3ʬɉ 4ɷ̎ŻʙȵɗJš-F/ƓdzGF3.̗Ȱʧ3Ǿ2ɷ̎ÒƦJʏ*' @̗ RsZM[„Żñŵȵɗ3ªȏŽǁȵɗJš'@3.F31D5̗Žǁ/3ˊ əJƦ+/.RsZM[„ŻñŵȵɗȯĢ2C*-ȍ 'Ĥä/úǑ3Ĥäʹ F/Ɠdz2ę,@3.F ɷ̎ÒƦ2C*-̗̈ːʍãJʨț!F'?2Ű ʖ1ĕØǻRsZM[„Îɧɨ/úǑ2§Š' 3ɘǀ4̗RsZM[„Żñ ŵȵɗďʺ2CF˅ʸŻʙȵɗ3ǖNJñĹč2Ľ!FƄתȏ4̗ł1/@˖Ñȝ 24̗ŽǁȵɗJš'@3.F/Jȱĉ-F ‡ƨ̗RsZM[„Żñŵ ȵɗȯĢcg.>DG'œ3̈ːˎã3na†„4̗ɷ̎ÒƦ.4ÊȊG1* ' %GB2̗RsZM[„Żñŵȵɗďʺ2CF̈ːʍãˎã3ŵʶAɴß2Ľ !Fʬɉǖǐ4̗ŽǁȵɗɎJš"2̗Ƹljŵ2½-F/ɪDGF
ƹɁ.4̗in vivo ̈ːˎãĶ̌ɎJȏ-̗̈ːʍãˎã2FRsZM[„Ż ñŵȵɗ/ÉĖȵɗDǐſGFŅƀîľɗʺ3ǖɴȝŨÞ2+-njʟ' %3 ɘǀ̗RsZM[„Żñŵȵɗďʺ4̗ŽǁȵɗɎİĖ-Fin vivo 3Ƽ Š.

ǖɴ-Ë̗ːʍãˎã3×ŭ2˪Œ-F/ƭD/1*' 3ȵɗ ďʺ2CFʬɉ2CE̗ȍ¨É.âȈC̈ːʍãˎãŞʹGF@3/ɪ DGF

42

Ʉ

Ʉ̜Ɂ

̈ːǔɐɆˎã2Ľ!FRsZM[„ŻñŵŅƀȵɗďʺ3

Ŷŕȝǖɴ3njʟ

ɡ
ʝ

̈ːǔɐɆˎã2Ľ-̗RsZM[„Żñŵȵɗďʺ03C1ŨÞJǀ'! njʟ!F'?2̗Ʉ̚Ɂ.4Žǁ/3ˊəJ³*'Ȅż.̈ː3ʍãˎãJʨț. Fin vivo 3Ķ̌ɎJȰɀ' ƧȍƯƵ2RsZM[„JƅŒ!F/.RsZM [„ŻñŵȵɗJȯĢ!F/Ķ̌ȝ2ôɴ.F3.̗Ʉ̛Ɂ.4in vivo 3Ķ̌ ɎJȏ-RsZM[„ŻñŵȵɗJȯĢ'RsZM[„Îɧɨ/ǿÎɧɨJǞʼ njʟ' ̈ːÉɺáĕØǻ2C*-ʍãˎãJʨț/H̗ǘŕcg.4ç‡ 3p†U.ƊɞƯ˩3ȫÉɺĕ3ĤäʠˡG'32Ľ-̗RsZM[„Żñ ŵȵɗȯĢcg.4˥ƊɞƯ˩J@*'ʕƢ3§p†UJƊ+ÉɺĕĤäʠ ˡG' 3/4̗RsZM[„Żñŵȵɗďʺ̈ːǔɐɆ3ïɥJɛù!F /2ĺŒ̗!5ÄːʍãˎãĶȊ̗Ƙð'̈ȂJâȈȝ2ȹˆ!F/ 2+1F/ɪDGF
RsZM[„ŻñŵȵɗȯĢcg2F@6/+3˝ʖ1ȩʗ4̗ǘŕc gCE@§ĕØǻ.ʍãˎãʨțG'/.F 3C1ȊʱʗÏG FȋȐ/-̗RsZM[„ŻñŵȵɗJʹǽ/!FƄ×ŵ3ȵɗďʺŶŕȝ2ǖ ɴ-E̗˅ʸȵɗ3ªȏ2Ɗɞȝ1Ƅ×J-FôɴŵɪDGF Ķ˵ 2̗RsZM[„Żñŵȵɗ4ʁțȝƊɞȝ2ǧŵäF/ěĀF̓Banik and Brennan, 2009; Rong et al., 2004̔ 3Ɗɞȝ1Ƅ×ĐĮ/-NO Ÿĵ G-F̗ƙÏǒƹ.ʜƿG'RsZM[„Żñŵȵɗďʺ3ǐſĐĮ36/+4

NO ªãŵȵɗ.F̓Ē̜; Boudaka et al., 2007; Izumi et al., 2003; Shiina et al., 2013; Shiina et al., 2012; Shiina et al., 2006̔ %GB2̗ÉĖȵɗ2C*-ùſ G'NO ˅ʸȵɗ3ªȏJŶŕȝ2Ƅ×-Fôɴŵ̏ Ÿ2̗3ȵɗďʺ Ŷŕȝ2ǖɴ-F3.G5̗RsZM[„ŻñŵȵɗȯĢG'RsZM [„ÎɧãȂ3̈ː3ïɥɴß4̗ǿÎɧãȂ3̈ːCE@̏/ɪDGF ‡ƨ̗ Ŷŕȝ1ªȏJƊ'13.G5̗RsZM[„Îɧɨ/ǿÎɧɨ/3˩.̗ïɥ ß2Ő414".F
%.̗ƹɁ3Ƞȝ4̗̈ːǔɐɆˎã2Ľ!FRsZM[„ŻñŵîľɗʺŶ ŕȝ2ǖɴ-F0JƭD2!F//' 3'?̗RsZM[„Î ɧcg/ǿÎɧcg3̈ːǔɐɆˎãJ̗ƙÏǒƹJȏ'in vitro Ķ̌.Ǟʼ '

44

ɘ

ɘ
ǀ

̓ ̚ ̔˅ ʸ ȵ ɗ Ø ǻ 2 C * - ʨ ț  G F  c g ̈ ː ǔ ɐ Ɇ 3 ï ɥ î Ų 2 Ľ ! F R s Z M [ „ 3 â ǀ
In vitro Ķ̌Ɏ̓Ē̛̔Jȏ-̗ǿÎɧC7RsZM[„ÎɧcgDƙÏ '̈ːǒƹ3ïɥîŲJdzĵ' ˺ǟØǻJá1Ȅż2Ft†]3îŲJ ʬ;'̗ʁțȝ1îŲ4ʧ?DG1*'̓ĒʑȤȖ̔ ˅ʸȵɗJ˺ǟØǻ'/ H̗ǿÎɧC7RsZM[„ÎɧcgȐƽ̈ː3"G2-@̗çïɥǑ3 îŲŞʹG'̓Ē̞̥̗̦̔̚ RsZM[„Żñŵȵɗ3ǧŵJȰʧ!F' ?̗RsZM[„3âǀJʬ;' RsZM[„30 µM J˓ȏ'/H̗ǿÎɧ cg̈ː3ïɥîŲ4Ƅ×G'̓Ē̞̥̔̚ 3Ƅ×4̗NO ùſ˚ɒ3˯ĸʌ. FL-NAME̓200 µM̔F4aTTi„ NK1 ñŨ3˯ĸʌ.F L-732,138 ̓2 µM̔3ÙƅŒ2CE̗ǰš'̓Ē̟̔̚ G4̗ƪě3ɘǀJÊȊ'@3. F ‡ƨ̗RsZM[„2CFïɥ3Ƅ×îŲ4̗RsZM[„Îɧcg̈ː.4 >DG1*'̓Ȩ̞̦̗̄̔̚ ̓ ̛ ̔ǿ Î ɧ  C 7 R s Z M [ „ Î ɧ  c g ̈ ː 2   F ˅ ʸ ȵ ɗ ŵ ï ɥ î Ų 2 Ľ ! F ˺ ǟ Ø ǻ Ƽ   3 Ĥ ä 3 ŧ ̀
RsZM[„Żñŵȵɗ˅ʸȵɗD3ȵɗ£ˑȂʶƟÏJŶŕȝ2Ƅ×- F0JƭD2!F'?̗˅ʸȵɗ˺ǟØǻƼ /îŲ3˪±2+-ʬ;' ØǻţśF4ØǻƊɞƯ˩J‰'/H̗%G2Ų -˅ʸȵɗŵïɥîŲ4 Ġţ'̓Ē̡̠̗̔̚̚ 3Ġţ2-̗ǿÎɧC7RsZM[„Îɧcg 3˩2ƴź1Őȗ4ʧ?DG1*'
˺ǟØǻ3̄śJĠá#'/H̗ǿÎɧC7RsZM[„Îɧcg̈ː/ @2̗úǑ3ţɥǑîŲʨțG'̓Ē̢̔̚ ţɥîŲ3ƳħƍŖ4ɨ˩.ƴź 1Ő4ʧ?DG1*'̓ǿÎɧ̣4.27 ± 0.87 g (n = 5) ̗RsZM[„Îɧ̣4.24 ±

0.96 g (n = 3)̔ ̓ ̓ ̜ ̔Ɇ Ęi X b „ ñ Ĺ ¨ Ƀ ù Ɖ Ɔ ʌ d-dvU€„3̈ːïɥîŲ2Ľ!FƄ× â ǀ
ǿÎɧC7RsZM[„Îɧcg̈ː2FȵɗɆƒù˖3ʌȋIJȝ1ȃŵ 2ŐȗF0Jnjʣ!F'?ɆĘiXb„ñŨɃùƉƆʌ d-dvU€ „3âǀJʬ;' d-dvU€„4ȏ˟®İȝ2˅ʸȵɗŵïɥîŲJƄ×'̓Ē ̛̙̥̔ ǿÎɧC7RsZM[„Îɧcg3˩2̗Ƅ×âǀ3ƴź1Őȗ4ʧ? DG1*'̓Ē̛̙̦̔ ̓ ̝ ̔ ˅ ʸ ȵ ɗ ˺ ǟ Ø ǻ 2 C F ̈ ː ǔ ɐ Ɇ ï ɥ î Ų 3 ȃ Ů
ǿÎɧC7RsZM[„Îɧcg̈ː2FǔɐɆïɥîŲ3ȃŵJǞʼ! F'?̗˅ʸȵɗØǻ2C*-ʨțGFçïɥǑîŲ3ǺƯ̗ƳħŢß=.3Ư˩ ïɥƊɞƯ˩Jʜƿ'̓Ē̛̥̔̚ RsZM[„Żñŵȵɗ3ȯĢ4̗GD3n {†a†2ƴź1ŧ̀JŒ1*'̓Ē̛̚b̗c̗d̔

46 Ē Ē ̚ ̞
ƙ Ï ̈ ː ǒ ƹ 2   F ˅ ʸ ȵ ɗ Ø ǻ 2 C F ï ɥ î Ų / R s Z M [ „ 3 ª ȏ ǿÎɧcg̥̓̔C7RsZM[„Îɧcg̦̓̔DƙÏ'̈ːǒƹJĒ̚2ȱ 'C1Ķ̌Ɏ2ʡɧ̗ʠˡ'ïɥîŲJȱ-F ˅ʸȵɗ:ç‡ȪťǤØǻ̓ØǻƊ ɞƯ˩100 µ ȸ̗Øǻ˺ĕ 80 V̔J̚Ñ˩˴.á'/H̗ǔɐɆçïɥǑ3îŲJʹ ' Ē4RsZM[„̓30 µM̔3˓ȏÙŪ3îŲ3ʑȝ1g‚†]Jȱ-F Ȩ̄ 4̗RsZM[„2CFïɥîŲ3Ƅ×ȈJʑ'Vq.F øVq3Ƣ¹4̗ŗė¹ SD .ȱ-F̓ǿÎɧɨ̣n = 3̗RsZM[„Îɧɨ̣n = 3̔ ̕4P < 0.05 .ɨ2ƴ źŐF/Jʑ-F

Ē ̚ ̟
R s Z M [ „ 3 Ƅ × ª ȏ 2 Ľ ! F NO ùſ˚ɒ˯ĸʌC7aTTi„ NK1 ñŨ˯ĸʌ3âǀ
ǿÎɧcgDƙÏ'̈ːǒƹ3˅ʸȵɗ:ç‡ȪťǤØǻ̓ØǻƊɞƯ˩100 µ ȸ̗ Øǻ˺ĕ80 V̔J̚Ñ˩˴.á-̗ǔɐɆ3çïɥǑ3îŲJŞʹ' Ē̥4RsZ M[„̓30 µM̔JçȅƅŒ̧̗̦̗4%G&G̗NO ùſ˚ɒ˯ĸʌ̓L-NAME̗200 µM̔ F4aTTi„NK1 ñŨ˯ĸʌ̓L-732,138̗2 µM̔JÙƅŒ'Ƽ Š.̗RsZM [„̓30 µM̔J˓ȏ'˵3ʑȝ1g‚†]Jȱ-F "G@RsZM[„2CFƄ ×âǀ4ǰš'

48 Ē Ē ̚ ̠
˅ ʸ ȵ ɗ 2 Ľ ! F ˺ ǟ Ø ǻ Ƽ   ̓ ˺ ĕ ̔ 3 Ĥ ä  ̈ ː ï ɥ î Ų 2 Œ  F ŧ ̀ Ē a 4̗ǿÎɧcgC7RsZM[„ÎɧcgDƙÏ'̈ːǒƹ3ïɥîŲ3 ʑȝ1g‚†]Jȱ-F ˅ʸȵɗ:ç‡ȪťǤØǻ̓ØǻƊɞƯ˩100 µ ȸ̗Øǻ˺ĕ ̚80 V̔J̚Ñ˩˴.á' Ē̦4̗Øǻ˺ĕ3Ġá2Ų 'ïɥŢß3ĤäJʑ'V q.F ïɥŢß4̗ƳħŢßJ 100%/'ȢĽ¹.ȱ-F øwM„g3Ƣ¹4̗ ŗė¹SD .ȱ-F̓ǿÎɧɨ̣n = 4̗RsZM[„Îɧɨ̣n = 4̔

Ē Ē ̚ ̡
˅ ʸ ȵ ɗ 2 Ľ ! F ˺ ǟ Ø ǻ Ƽ   ̓ Ɗ ɞ Ư ˩ ̔ 3 Ĥ ä  ̈ ː ï ɥ î Ų 2 Œ  F ŧ ̀ ǿÎɧcgC7RsZM[„ÎɧcgDƙÏ'̈ːǒƹ2-̗˅ʸȵɗ:ç‡ ȪťǤØǻ̓ØǻƊɞƯ˩10100 µ ȸ̗Øǻ˺ĕ 80 V̔J̚Ñ˩˴.á' Ē4̗ØǻƊ ɞƯ˩3Ġá2Ų 'ïɥŢß3ĤäJʑ'Vq.F ïɥŢß4̗ƳħŢßJ100%/ 'ȢĽ¹.ȱ-F øwM„g3Ƣ¹4̗ŗė¹SD .ȱ-F̓ǿÎɧɨ̣n = 4̗ RsZM[„Îɧɨ̣n = 4̔

50 Ē Ē ̚ ̢
˅ ʸ ȵ ɗ 2 Ľ ! F ˺ ǟ Ø ǻ Ƽ   ̓ Ø ǻ ̄ ś ̔ 3 Ĥ ä  ̈ ː ï ɥ î Ų 2 Œ  F ŧ ̀ Ē4̗ǿÎɧcgC7RsZM[„ÎɧcgDƙÏ'̈ːǒƹ3ïɥîŲ3ʑȝ 1g‚†]Jȱ-F ˅ʸȵɗ:Ħn]3ȪťǤØǻ̓ØǻƊɞƯ˩100 µ ȸ̗Øǻ˺ ĕ80 V̗ØǻƯ˩ 5 ȸ̔Já̗%3̄śJ 1~50 Hz =.Ĥä#'

Ē Ē ̛ ̙
̈ ː ǒ ƹ 2   F ˅ ʸ ȵ ɗ ŵ ï ɥ î Ų 2 Ľ ! F D-dvU€„3âǀ Ē a 4̗ǿÎɧcgC7RsZM[„ÎɧcgDƙÏ'̈ːǒƹ3˅ʸȵɗŵï ɥîŲ2Ľ!F D-dvU€„̓0.55 µM̔3âǀJȱ'ʑȝ1g‚†].F ˅ʸ ȵɗ:4ç‡ȪťǤØǻ̓ØǻƊɞƯ˩100 µ ȸ̗Øǻ˺ĕ 80 V̔J̚Ñ˩˴.á' Ē̦ 4̗D-dvU€„̓0.55 µM̔3ïɥîŲ2Ľ!FƄ×âǀJʑ'Vq.F ïɥŢ ß4̗ƳħŢßJ100%/'ȢĽ¹.ȱ-F øwM„g3Ƣ¹4̗ŗė¹SD .ȱ -F̓ǿÎɧɨ̣n = 4̗RsZM[„Îɧɨ̣n = 4̔

52 Ē Ē ̛ ̚
̈ ː ǒ ƹ 2   F ˅ ʸ ȵ ɗ ŵ ï ɥ î Ų 3 ȃ ŵ
Ē a 4̗ǿÎɧcgC7RsZM[„ÎɧcgDƙÏ'̈ːǒƹ3˅ʸȵɗŵï ɥîŲ3ʑȝ1g‚†].F é4̗˅ʸȵɗ:3˺ǟØǻ̓ç‡ȪťǤØạ̊́ØǻƊɞ Ư˩100 µ ȸ̗Øǻ˺ĕ 80 V̔3aMy„VJȱ-F Ē̥Ž3̦̗c̗d,JØǻDîŲ J˨ī!F=.3ǺƯ̗ƳħŢß2ˑ!F=.3Ư˩̗ïɥƊɞƯ˩/-ʞdz̗%G&GĒ ̦’̧̗’̨̗’2-Vq/-ȱ' øVq3Ƣ¹4̗ŗė¹SD .ȱ-F̓ǿÎɧ ɨ̣n = 5̗RsZM[„Îɧɨ̣n = 3̔

ɪ

ɪ
Ļ

ƹɁ.4̗RsZM[„ŻñŵȵɗJʹǽ/!FȵɗďʺŶŕȝ2Ƅ×ŵ3ʬɉ J-F0JƭD2!F'?̗RsZM[„ŻñŵȵɗȯĢcgJªÏ ̗ǿÎɧ̓ǘŕ̔cg3̈ːǔɐɆïɥˎã/Ǟʼnjʟ' @̗RsZM[„ ŻñŵȵɗŶŕȝ2ǖɴ-F3.G5̗ȵɗ3ȯĢ2C*-̗˅ʸȵɗD 3£ˑȂʶƟÏ3Ƅ×ʜ˲G̗ǘŕ1̈ː/Ǟʼ-̗CEţß1̈ːǔɐɆ3 ïɥîŲʠˡGF/(H ‡ƨ̗RsZM[„ŻñŵȵɗŶŕȝ2ǖɴ# "̗©D3Øǻ2C*-ǧŵä!F3.G5̗Żʙȵɗ2Ľ!FØǻJŒ1 ˰E̗ȵɗJȯĢ-@Ĥäʹ1/F Ķ˵2ŬDG'ɘǀ4̗ǿÎɧ C7RsZM[„Îɧcg3̈ːˎã2-̗ƴź1ŐȗİĖ1/@ 3.*' RsZM[„ÎɧcgȐƽ3̈ːǒƹ2FïɥîŲ4̗RsZM [„˓ȏ2Ľ-̆ʉ1Ƅ×îŲJȱ1*'/D̗ƧȍĮƵ3RsZM[„ Îɧ2CFŻʙȵɗȯĢ4ſà-'/F '*-̗ƹɁ3ɘǀ4Rs ZM[„Żñŵȵɗďʺ4Ŷŕȝ2ǧŵä-F3.41̗©D3Øǻ2Ų -ǧŵä!F@3.F/Jȱĉ-F
@̗RsZM[„ŻñŵȵɗďʺŶŕȝ2ǧŵä-F3.G5̗ǿÎɧ cg3̈ː2F˅ʸȵɗD3ȵɗ£ˑȂʶ3ƟÏ˟4̗RsZM[„Îɧ cg̈ː2F%GCE@Ł/Ɠdz.F 3Ɠdz2ę,̗˅ʸȵɗØǻ Ƽ /îŲ3˪±2+-ʬ;' ȵɗ£ˑȂʶ3ƟÏ4Øǻ3ţ2Ų -Ĥä! F'?̗3ƓdzǘG5̗ØǻƼ 3Ĥä2Ų 'îŲ3Ĥä2ɨ˩.Ő ȍ F4".F 1D̗˺ǟØǻţśAØǻƊɞƯ˩3Ġá2¤*'îŲ 3Ġţ4̗ɨ˩.úǑ.*' 3ɘǀ4̗RsZM[„Żñŵȵɗ4Ŷŕȝ2 ǧŵäG-F3.41̗'(İĖ!F(.4˅ʸȵɗD3ȵɗ£ˑȂʶƟ ÏJƄ×!F24ʂD1/Jȱĉ-F RsZM[„ŻñŵȵɗŶŕȝ2 ǖɴ-1/ƀʗ4̗d-dvU€„Jȏ'Ķ̌D@úǑ2ƓĻGF

54

d-dvU€„4L_bX€„ñŨ2Ľ!FɃùƉƆʌ.F3.̗3ʌȂ3â ǀ3˒4̗L_bX€„3ƟÏ˟3˒JîƮ'@3.F/F(H ̓Jonsson et al., 2009̔ 1D̗d-dvU€„3ïɥƄ×âǀ4̗ɨ˩. Ő1*' GD3ɘǀ4̗RsZM[„ŻñŵȵɗďʺŶŕȝ2˅ʸȵɗD 3L_bX€„ƟÏJƄ×-F3.41/Jȱĉ-F
Ǘ2̗RsZM[„Żñŵȵɗďʺ̗Ɇɔɲ‰3ñŨ3ŠǨ2¦ɧ!FɔɲÉ. 3Mt„g2˪Œ-Fôɴŵ2+-njʟ' @̗3C1×ŭʹ*-F/!G5̗˅ʸȵɗŵïɥîŲ3ȃŵ̗¬5̗ǺƯAƳħïɥ=.3ƀʖƯ˩̗ ïɥƊɞƯ˩̗RsZM[„Żñŵȵɗ3ȯĢ2C*-Ĥä!F/’Ÿ.F D 2̗ïɥ3á˝4ɔɲÉ3Ca2+_{3ʋȼ2®İ!F̓Nogueira and Hogan, 2010̔/} D̗̄ď˺ǟØǻ2C*-ʨŀGFţɥîŲ@ȵɗȯĢ2CEĤä!F(H  1D̗RsZM[„ŻñŵȵɗJȯĢ-@̗GD3ïɥȃŵ2ƴź1Ĥä4 >DG1*' ž‰3ɘǀD@̗Ɇɔɲ%3@33ïɥȃŵ2Ľ-@̗RsZM [„Żñŵȵɗ4Ŷŕȝ1ŧ̀JŒ-41/F
RsZM[„ŻñŵŅƀȵɗďʺ2CF̈ːǔɐɆ3ˎãʬɉǖǐ4̗Ŷŕȝ2ǖ ɴ-F3.41̗©D3ʖĐ2C*-RsZM[„ŻñŵȵɗǧŵäG F˵24 ?-ǖɴ!F/ɪDGF Ķ̌ȝ2«ȏG-FØǻ4RsZM[„A pu€„103ʌÜ.F̗G4=.@ȭȽȏ3d†.E̗ȍȋȝ1ǧŵ äʖĐ.41/4ƭȜ.F 3ǧŵäJŞʹ!ȍȋȝ1Øǻ/-̗̈ː ÉɺD3¥ŇØǻɪDGF Ķ˵̗RsZM[„ŻñŵȵɗJþ?'c ɢɟ¥ ŇF4ĕØǻ2C*-ǧŵäGF/Jȱ!+3ȭȽɘǀěĀG-F̓Aizawa et al., 2011; De Groat et al., 1982; Yu et al., 2009̔ ƹɁ3ȭȽ4̗ƙ Ï̈ːǒƹJȏ'in vitro Ķ̌Jt†]2'@3.Ë̗ːʍãˎã3țȊ2/ *-Ű́3ŽǁȵɗɎ1Ȅż.ʏ*'@3.F RsZM[„Żñŵȵɗďʺ ǧŵä!F24̗ŽǁȵɗɎ/3ˊəˢ21F3@G1 3ȵɗďʺ3×ŭ ǖǐJƑF'?24̗ŽǁȵɗɎİĖ!FC1̗CEȍ¨É2˃Ȅż.3Ķ̌

Űʖ/1F/F
ƹɁ.4̗̈ːǔɐɆˎãJ×ŭ!FRsZM[„ŻñŵȵɗďʺŶŕȝ2ǖɴ F@3.F0J̗ƙÏ̈ːǒƹJȏ'Ķ̌2CEnjʟ' ŬDG' ȩʗD̗Ņƀȵɗďʺ2CF̈ːˎãʬɉǖǐ4Ŷŕȝ2ǖɴ-[email protected] ̗ʬɉǖǐ3ǧŵäJ²!'?2̗©D3ØǻAŽǁȵɗɎ/3ˊəŰʖ.F /ȱĉG'

56

ɠ

ɠ

ù ɪ Ļ

ƹȭȽ4̗̈ːǔɐɆ˖3ʍãˎã2Ľ-̗RsZM[„Żñŵȵɗ/ÉĖȵɗ ɎDǐſGFŅƀȵɗďʺ03C1ǖɴȝŨÞJ@*-F3̗%3ʜƭ JȠƋ-1*'
̈ː2FRsZM[„Żñŵȵɗ/ÉĖȵɗɎDǐſGFŅƀȵɗďʺ4 @/@/̗ƙÏ̈ːǒƹJȏ'in vitro Ķ̌Ɏ2CE̗ƭD2G'@3.F ̓Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2012; Shiina et al., 2006̔ ŻʙȵɗØǻʌ.FRsZM[„3˓ȏ2C*-̈ːǔɐɆˎ ã3ïɥߧŠ'//̗RsZM[„3ªȏNO ùſ˚ɒ˯ĸʌC7aTT i„ñŨ˯ĸʌ2C*-ǰš'/D̗RsZM[„Żñŵȵɗǧŵä!F/̗ %DaTTi„ƟÏG̗3aTTi„NO ªãŵÉĖȵɗJØǻ!F/ .ƟÏG'NO ˅ʸȵɗƸɂ2ªȏ-L_bX€„ƟÏJƄ×!F/.̗̈ ːǔɐɆïɥƄ×GF̗/*'ŅƀȵɗîľɗʺƔċG'̓Ē̜̔ 3Ÿ ʪ4̗ÉĖȵɗ/˅ʸȵɗƸɂ/ÇŅĖ!F/ťżIJȝ1f†aD@ƝƊG F@3.F̓Neuhuber et al., 2006; Wörl and Neuhuber 2005̔ ƹȭȽ3 in vivo ̈ːˎã3ʜƿ2CE̗3RsZM[„Żñŵȵɗďʺ4̗̈ːǔɐɆ˖3ʍãˎã 3×ŭ2˪Œ-F/ƭD/1*'
RsZM[„Żñŵȵɗďʺ2CF̈ːʍãˎã3×ŭ3›ƨ4̗8'+F/ɪ DGF 6/+4̗ɛùG'ßţʍãˎã3ĶȊ.F 3ȵɗîľɗʺǧŵ GF/̗̈ːǔɐɆ3ïɥß4Ƅ×GF/’ŸGF %3'?̗3ȵɗďʺ4̗ ̈ː2-ʍãˎãʨțGF˵2̗˓ś2Ƅ×J++̗Űʖ2Ų -%GJ ʜ˲!F/.̗ïɥ3aMy„VJI#̗%3ɘǀ/-ßţʍãˎãʹ F3@G1 ̈ː3Ɇň4̗Éĥ̛ň2ÑG-F̓Neuhuber et al., 2006; Wörl and Neuhuber 2005̔ 3̛ň3ïɥŠɣ3aMy„Vʍãˎã2/*-˽ ŕ2˝ʖ.F/̗ŁɻAħɻ.4ěĀG-F̓Furness, 2006; Hansen, 2003;

Leonard et al., 2006; Olsson and Holmgren, 2011̔ ̈ː2-@úǑ3ǖǐF @3/ŴIGF̗%3ěĀ41 ̛ň3Ɇň3ïɥŠɣ3aMy„V4̗ïɥJ÷ Fʄĩŵȵɗ(.1̗ŠɣJ÷FƄ×ŵȵɗ2C*-@ʬɉGF̓Furness, 2006; Hansen, 2003; Leonard et al., 2006; Olsson and Holmgren, 2011̔ %3'?̗ RsZM[„Żñŵȵɗďʺ2CFƄ×ŵʬɉ̗3Éĥ̛ň3Ɇň3ïɥaMy„ V3ʬɉ2˪Œ-FôɴŵF Ķ˵̗ƙÏǒƹ3Ķ̌.̗ɤʸƨü3ˎã2@ ʽʸƨü3ˎã2@̗RsZM[„ŻñŵŅƀîľɗʺ½-F/ȱG- F̓Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2012; Shiina et al., 2006̔
@6/+4̗˅ʸŻʙȵɗ3ǖNJñĹč3Żñŵ2Ľ!FƄתȏ.F ƙÏǒ ƹJȏ'Ķ̌.4̗ǖNJñĹč3Żñŵ4ʤ¯.1 D2̗ŽǁȵɗɎJš '@3@F/ɪDGF'?̗3ªȏțʗ.'34̗in vivo Ķ̌Ɏ3ȃŵJ ȍ'ƹȭȽ3ħ1ſǀ.F RsZM[„ŻñŵȵɗȯĢcg/ɷ̎ÒƦ cg2F̈ːʍãˎãJʨț!FĕØǻ3ˬ¹/@2§Š'/D̗3ª ȏ2ɷ̎F4%GCE@‰¦3ŽǁȵɗŰ́.F/ɪDGF 1D̗ Ȩȝ1›ɖ>3ʜƭ3'?24̗D1FȭȽŰʖ.F
ƙÏǒƹ2-4̗RsZM[„ŻñŵŅƀȵɗďʺ4Ŷŕȝ2ǖɴ-FI .1̗RsZM[„/*'ŻʙȵɗØǻʌ2CFĥ˖D3ǧŵäĐĮFȄǢ Š.̗%3ǖɴțƖGF̓Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2012; Shiina et al., 2006̔ ‡ƨ̗in vivo Ķ̌Ɏ.4̗ĥ˖D3 ȃÕ1Øǻ1.̗RsZM[„ŻñŵŅƀȵɗďʺǖɴ-FC.F ( D%̗RsZM[„Żñŵȵɗ3ȯĢ2CFâǀ4̗%3ȵɗ3ǖɴJȱĉ-' 3in vitro / in vivo 2Fªȏ3˒4̗03C2ʪƭ.F(H ǖNJ ñĹč3Żñŵ2Ľ!FƄתȏ2+-4̗ŽǁȵɗŰ́/1F/ɪDGF'?̗ ŽǁȵɗɎ/3ˊəİĖ!Fin vivo /%GƦ'G' in vitro /.ȗ1Fɘǀȍ '/-@©Dȧȣ41(H

58

‡ƨ̗ɛùG'ßţʍãˎã2Ľ!Fªȏ2+-4̗Ƹlj.3ǔɐɆïɥîŲ 3Ƅ×.ʪƭôɴ.F %3'?̗in vivo 2-4̗1KD3ȋȐ2CE̗ RsZM[„ŻñŵȵɗǧŵäGF/’ŸGF 6/+3ôɴŵ4̗Rs ZM[„Żñŵȵɗ3ʁțȝ1ǧŵä.F @6/+3ôɴŵ4̗ǧŵäJŞ ʹ!ʖĐ3İĖ.F %3ƴß1¸ʓĐĮ4̗̈ːġ:3ˌŇØǻ.F Rs ZM[„Żñŵȵɗ4̗°ĸ‚t3ţ¥Ň2îŲ!F̏ˬ¹̓> 30 mmHg̔3Ż ʙȵɗ.F̓Spencer et al., 2008; Yu et al., 2005̔ 1D̗ƹȭȽ.á 'Éɺ:3ĕØǻ3ħ4̗Ƴħ8 mmHg =..E̗RsZM[„Żñŵȵɗ3 ˬ¹=.ņ1‚t.1 ̗ǿÎɧ3@3/RsZM[„Żñŵȵ ɗ3ȯĢJ'@3.̗ʍãˎã3ɴß2ŐDIG' ƹȭȽ.dzĵG'̈ː Éɺĕ4̗̈ːDˆEÏG'ǭ¨2CFɠ¨ȝ1ĕß.Ë̗ːġŅƀ.3ĕ ß4ʞdzG-1 %3'?̗@̈ːġ:3¥ŇØǻRsZM[„Żñŵȵ ɗ3ǧŵäJŞʹ!3.F31D̗x€QcgvgD3ĕØǻ2á-̗ ̈ːɆ3ïɥ̗Ņƀ.3¥ŇØǻ3‰Ƭ2ĺŒ̗%GRsZM[„Żñŵȵɗ Jǧŵä.Fˬ¹‚t.*'/ɪF3ĪŤ.H %ɪF/̗Rs ZM[„Żñŵȵɗďʺ4̗̈ːǔɐɆţïɥ!F˖¦̗!1I)Éɺ2̈Ȃ İĖ̗ʍãǤțȍ!Fɇƀ.ǖɴ!F/21F G4̗3ȵɗďʺʍã ˎã3ɛùJĶȊ!F/Ÿʪ/‡ʃ!F ̈ːġ:3¥ŇØǻRsZM[„Ż ñŵȵɗ3ǧŵäJŞʹ!/țŸ4̗‡ĵ3ùȋŵF/F(H
ž‰̗ƹȭȽ2CË̗ːǔɐɆˎã2Ľ!FÉĖȵɗJþ?'RsZM[„Żñŵ ȵɗďʺ3ǖɴȝŨÞJʜƭ!F/.' 6/+4̗ŽǁȵɗɎJš'˅ʸŻ ʙȵɗ3ǖNJñĹč3Żñŵ3Ƅ×ŵ×ŭ.E̗@6/+4Ƹlj‚t.ªȏț ƖGFʍãˎã3ɛù2Ľ!Fªȏ.F GD3ªȏ2CE̗Ƙð'̈ȂJó ɺDɰ¼:/âȈȝ2ˎ9̈ːʍãˎãĶȊGF3@G1

ʮ

ʮ
ˀ

ƹȭȽ3ˍʏ1D72ƹʭƤ3ªſ2'E̗ƋŀƠć/-̗ɕīžɊ1F Ƌŀ/˿ƛJʵE='̗ʼn˭ħIJħIJ˱ˊùȇåIJȭȽȷƠƐ
űǠǦǙèģ̓ʼn ˭ħIJ̔2ǮŻʮȑ‰=!
ƹʭƤ3ʇȻJdž˫-(E='̗ʼn˭ħIJħIJ˱ˊùȇåIJȭȽȷƠƐ
Ȭ•Öƭèģ̓ŔŚȕȎħIJ̗̔ƶŌư‡˕èģ̓ŋƁħIJ̔DZ˂Áèģ̓ƾ—ˁŎħ IJ̗̔Ǫ˞Řşèģ̓ʼn˭ħIJ̔2ʯK.Żʮ3źJʑ=!
ƹȭȽ3ˍʏ2'E̗ŭƋŀʵE='̗ʼn˭ħIJûʦƠƐ
Ǚɵɩèģ̗ʼn˭ ħIJħIJ˱ˊùȇåIJȭȽȷÍƠƐ
NjûʴŦèģ̗ŋƁħIJûʦƠƐ
ǕȀ‡Čè ģ2Żʮȑ‰=!
='̗ƹȭȽ2˵-Ħħ1æßJ(E='ʼn˭ħIJȇåȍȋIJȭȽķ3 ȞǑ2ůCEŭȲȑ‰=!
ƳŪ2̗ƹȭȽ2ĿĄJƏ-ŠE='ƢĦ3Ķ̌ãȂ3ÌȶJȴE '=!

60

Ş

Ş
ȏ
Ƥ
Ȇ

Aizawa, N., Igawa, Y., Nishizawa, O. and Wyndaele, J.J. (2011). Effects of nitric oxide on the primary bladder afferent activities of the rat with and without intravesical acrolein treatment. Eur. Urol. 59, 264~271.

Andrew, B.L. (1956). The nervous control of the cervical oesophagus of the rat during swallowing. J. Physiol. 134, 729~740.

Banik, R.K. and Brennan, T.J. (2009). Trpv1 mediates spontaneous firing and heat sensitization of cutaneous primary afferents after plantar incision. Pain 141, 41~51.

Berthoud, H.R., Patterson, L.M., Neumann, F. and Neuhuber, W.L. (1997a). Distribution and structure of vagal afferent intraganglionic laminar endings (IGLEs) in the rat gastrointestinal tract. Anat. Embryol. (Berl). 195, 183~191.

Berthoud, H.R., Patterson, L.M., Willing, A.E., Mueller, K. and Neuhuber, W.L. (1997b). Capsaicin-resistant vagal afferent fibers in the rat gastrointestinal tract: anatomical identification and functional integrity. Brain Res. 746, 195~206.

Bieger, D. and Neuhuber, W.L. (2006). Neural circuits and mediators regulating swallowing in the brainstem. GI Motility online: doi:10.1038/gimo1074.

Boudaka, A., Wörl, J., Shiina, T., Neuhuber, W.L., Kobayashi, H., Shimizu, Y. and Takewaki, T. (2007). Involvement of TRPV1-dependent and -independent

esophagus. Eur. J. Pharmacol. 556, 157~165.

Boudaka, A., Wörl, J., Shiina, T., Shimizu, Y., Takewaki, T. and Neuhuber, W. L. (2009). Galanin modulates vagally induced contractions in the mouse oesophagus. Neurogastroenterol. Motil. 21, 180~188.

Bogeski, G., Shafton, A.D., Kitchener, P.D., Ferens, D.M. and Furness, J.B. (2005). A quantitative approach to recording peristaltic activity from segments of rat small intestine in vivo. Neurogastroenterol. Motil. 17, 262~272.

Broussard, D.L., Li, X. and Altschuler, S.M. (1996). Localization of GABAA alpha 1 mRNA subunit in the brainstem nuclei controlling esophageal peristalsis. Brain Res. Mol. Brain Res. 40, 143~147.

Broussard, D.L., Wiedner, E.B., Li, X. and Altschuler, S.M. (1994). NMDAR1 mRNA expression in the brainstem circuit controlling esophageal peristalsis. Brain Res. Mol. Brain Res. 27, 329~332.

Ciccocioppo, R., Onori, L., Messori, E., Candura, S.M., Coccini, T. and Tonini, M. (1994). Role of nitric oxide-dependent and -independent mechanisms in peristalsis and accommodation in the rabbit distal colon. J. Pharmacol. Exp. Ther. 270, 929~937.

Clouse, R.E. and Diamant, N.E. (2006). Motor Function of the Esophagus. In: Johnson, L.R. (Ed.), Physiology of the gastrointestinal tract, 4th ed. pp. 913~926. Elsevier Academic Press, Burlington.

62

Cunningham, E.T. Jr. and Sawchenko, P.E. (1990). Central neural control of esophageal motility: a review. Dysphagia 5, 35~51.

De Groat, W.C., Booth, A.M., Milne, R.J. and Roppolo, J.R. (1982). Parasympathetic preganglionic neurons in the sacral spinal cord. J. Auton. Nerv. Syst. 5, 23~43.

Furness, J.B. (2006). The Enteric Nervous System. Blackwell Publishing, Oxford.

Geppetti, P. and Trevisani, M. (2004). Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function. Br. J. Pharmacol. 141, 1313~1320.

Goyal, R.K. and Chaudhury, A. (2008). Physiology of normal esophageal motility. J. Clin. Gastroenterol. 42, 610~619.

Hansen, M. B. (2003). Neurohumoral control of gastrointestinal motility. Physiol. Res. 52, 1~30.

Hashim, M.A. and Bieger, D. (1989). Excitatory amino acid receptor-mediated activation of solitarial deglutitive loci. Neuropharmacology 28, 913~921.

Holzer, P. (1988). Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 24, 739~768.

Holzer, P. (1991). Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol. Rev. 43, 143~201.

Holzer, P. (2004). TRPV1 and the gut: from a tasty receptor for a painful vanilloid to a key player in hyperalgesia. Eur. J. Pharmacol. 500, 231~241.

Izumi, N., Matsuyama, H., Ko, M., Shimizu, Y. and Takewaki, T. (2003). Role of intrinsic nitrergic neurones on vagally mediated striated muscle contractions in the hamster oesophagus. J. Physiol. 551, 287~294.

Jean, A. (2001). Brain stem control of swallowing: neuronal network and cellular mechanisms. Physiol. Reviews 81, 929~969.

Jonsson Fagerlund, M., Dabrowski, M. and Eriksson, L.I. (2009). Pharmacological characteristics of the inhibition of nondepolarizing neuromuscular blocking agents at human adult muscle nicotinic acetylcholine receptor. Anesthesiology 110, 1244~1252.

Leonard, R.J., Kim, E.B., Fayez, K.G., Juanita, L.M., Hamid, M.S. and Jackie, D.W. (2006). Physiology of the gastrointestinal tract. Volume 1. Fourth editon. In : Jackie, D.W. Integrative functions of the enteric nervous system, 4th ed., pp. 670~672. Academic Press, Burlington.

Loomis, C.W., Yao, D. and Bieger, D. (1997). Characterization of an

64

Lu, W.Y. and Bieger, D. (1998). Vagovagal reflex motility patterns of the rat esophagus. Am. J. Physiol. Regul. Integr. Comp. Physiol. 274, R1425~1435.

Masliukov, P.M, Moiseev, K.Y., Korzina, M.B. and Porseva, V.V. (2015).

Development of nNOS-positive neurons in the rat sensory ganglia after capsaicin treatment. Brain res. 1618 212~221

Neuhuber, W.L., Raab, M., Berthoud, H.R. and Wörl, J. (2006). Innervation of the mammalian esophagus. Advances in Anatomy, Embryology, and Cell Biology 185, 1~73.

Nogueira, L. and Hogan, M.C. (2010). Phenol increases intracellular [Ca2+] during twitch contractions in intact Xenopus skeletal myofibers. J. Appl. Physiol. (1985). 109, 1384~1393.

Olsson, C. and Holmgren, S. (2011). Autonomic control of gut motility: A comparative view. Auton. Neurosci. : Basic & Clinical 165, 80~101.

Onori, L., Aggio, A., Taddei, G., Loreto, M.F., Ciccocioppo, R., Vicini, R., Tonini, M., 2003. Peristalsis regulation by tachykinin NK1 receptors in the rabbit isolated distal colon. Am. J. Physiol. 285, G325-331.

Page, A.J., O'Donnell, T.A., Cooper, N.J., Young, R.L. and Blackshaw, L.A. (2009). Nitric oxide as an endogenous peripheral modulator of visceral sensory neuronal function. J. Neurosci. 29, 7246~7255.

Patterson, L.M., Zheng, H., Ward, S.M. and Berthoud, H.R. (2003). Vanilloid receptor (VR1) expression in vagal afferent neurons innervating the

gastrointestinal tract. Cell Tissue Res. 311, 277~287.

Phillips, R.J. and Powley, T.L. (2000). Tension and stretch receptors in gastrointestinal smooth muscle: re-evaluating vagal mechanoreceptor electrophysiology. Brain Res. Brain Res. Rev. 34, 1-26.

Rong, W., Hillsley, K., Davis, J.B., Hicks, G., Winchester, W.J. and Grundy, D. (2004). Jejunal afferent nerve sensitivity in wild-type and TRPV1 knockout mice. J. Physiol. 560, 867~881.

Sang, Q. and Goyal, R.K. (2001). Swallowing reflex and brain stem neurons activated by superior laryngeal nerve stimulation in the mouse. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G191~200.

Sasamura, T. and Kuraishi, Y. (1999). Peripheral and central actions of capsaicin and VR1 receptor. Jap. J. Pharmacol. 80, 275~280.

Satchell, PM. (1984). Canine oesophageal mechanoreceptors. J. Physiol. 346, 287~300.

Sengupta, J.N. (2000). An overview of esophageal sensory receptors. Am. J. Med. 108 Suppl 4a, 87S~89S.

66

sensory and motor functions of the esophagus. Am. J. Med. 111 Suppl 8A, 169S-173S.

Shiina, T., Shima, T., Suzuki, Y. and Shimizu, Y. (2013). Inhibitory actions of a local neural reflex on propulsive activity of the esophageal striated muscle portion in rats. Res. Vet. Sci. 94, 331~335.

Shiina, T., Shima, T., Suzuki, Y., Wörl, J. and Shimizu, Y. (2012). Neural regulation of esophageal striated muscle in the house musk shrew (Suncus murinus). Auton. Neurosci. 168, 25~31.

Shiina, T., Shimizu, Y., Boudaka, A., Wörl, J. and Takewaki, T. (2006). Tachykinins are involved in local reflex modulation of vagally mediated striated muscle

contractions in the rat esophagus via tachykinin NK1 receptors. Neuroscience 139, 495~503.

Shiina, T., Shimizu, Y., Suzuki, Y., Nikami, H. and Takewaki, T. (2005).

Measurement of the propelled liquid by isolated hamster ileum as a parameter to evaluate peristalsis. Eur. J. Pharmacol. 517, 120~126.

Shimizu, Y., Chang, E.C., Shafton, A.D., Ferens, D.M., Sanger, G.J., Witherington, J. and Furness, J.B. (2006). Evidence that stimulation of ghrelin receptors in the spinal cord initiates propulsive activity in the colon of the rat. J. Physiol. 576, 329~338.

longitudinal and circular muscle during peristalsis in the isolated guinea-pig distal colon. J. Physiol. 506, 563~577.

Spencer, N.J., Kerrin, A., Singer, C.A., Hennig, G.W., Gerthoffer, W.T. and

McDonnell, O. (2008). Identification of capsaicin-sensitive rectal mechanoreceptors activated by rectal distension in mice. Neuroscience 153, 518~534.

Suzuki, N., Mizuno, K. and Gomi, Y. (1994). Role of nitric oxide in the peristalsis in the isolated guinea-pig ileum. Eur. J. Pharmacol. 25, 221~227.

Szallasi, A. and Blumberg, P.M. (1999). Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol. Rev. 51, 159~212.

Szolcsanyi, J. and Bartho, L. (2001). Capsaicin-sensitive afferents and their role in gastroprotection: an update. J. Physiol. Paris. 95, 181~188.

Tominaga, M. and Tominaga, T. (2005). Structure and function of TRPV1. Pflügers Archiv : Eur. J. Physiol. 451, 143~150.

Tsuda, M., Koizumi, S., Kita, A., Shigemoto, Y., Ueno, S. and Inoue, K. (2000). Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats: involvement of heteromeric P2X2/3 receptor signaling in capsaicin-insensitive primary afferent neurons. J. Neurosci. 20, RC90.

Wang, Y.T. and Bieger, D. (1991). Role of solitarial GABAergic mechanisms in control of swallowing. Am. J. Physiol. 261, R639~646.

68

Waterman, S.A. and Costa, M. (1994). The role of enteric inhibitory motoneurons in peristalsis in the isolated guinea-pig small intestine. J. Physiol. 477, 459-468

Wörl, J. and Neuhuber, W.L. (2005). Enteric co-innervation of motor endplates in the esophagus: state of the art ten years after. Histochem. Cell Biol. 123, 117~130.

Yamashita, H., Wang, Z., Wang, Y., Furuyama, T., Kontani, Y., Sato, Y. and Mori, N. (2008). Impaired basal thermal homeostasis in rats lacking capsaicin-sensitive peripheral small sensory neurons. J. Biochem. 143, 385~393.

Yu, S., Gao, G., Peterson, B.Z. and Ouyang, A. (2009). TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus. Am. J. Physiol. Gastrointest. Liver Physiol. 297, G34~42.

Yu, S., Undem, B.J. and Kollarik, M. (2005). Vagal afferent nerves with nociceptive properties in guinea-pig oesophagus. J. Physiol. 563, 831~842.

Zagorodnyuk, V.P. and Brookes, S.J. (2000). Transduction sites of vagal mechanoreceptors in the guinea pig esophagus. J. Neurosci. 20, 6249~6255.