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/20.500.1209 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
3 4 7 1 in vivo 15 19 27 2 30 31 38 3 42 44 53 56 59 60 2
SD standard deviation L-NAME N G -nitro-l-arginine methyl ester TRPV1 transient receptor potential cation channel, subfamily V, member 1 NO nitric oxide 3
Furness, 2006; Hansen, 2003; Leonard et al., 2006; Olsson and Holmgren, 2011 Furness, 2006; Hansen, 2003; Leonard et al., 2006; Olsson and Holmgren, 2011 Furness, 2006; Hansen, 2003; Leonard et al., 2006; Olsson and Holmgren, 2011 Ciccocioppo et al., 1994; Onori et al., 2003; Shiina et al., 2005; Smith and Robertson, 1998; Suzuki et al., 1994; Waterman and Costa, 1994 - Andrew, 1956; Clouse and Diamant, 2006; Cunningham and Sawchenko, 1990; Goyal and Chaudhury, 2008; Jean, 2001; Lu and Bieger, 1998; Neuhuber et al., 2006 Shiina et al., 2013 4
Neuhuber et al., 2006; Wörl and Neuhuber, 2005 Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2006; Shiina et al., 2012 transient receptor potential cation channel, subfamily V, member 1 TRPV1 Holzer, 1988; Holzer, 1991; Holzer, 2004; Geppetti and Trevisani, 2004; Tominaga and Tominaga, 2005 Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2012; Shiina et al., 2006 in vivo in vivo in vitro 5
6
14 17 Wistar 400-600 g 10 12 Sprague-Dawley 300-350 g SLC 22 ± 2 12 12 7 00 19 00 LABO MR Stock MF α- α- 10% 2-Hydroxypropyl- -cyclodextrin 0.9% NaCl NaCl 118.4 mm, KCl 4.7 mm, CaCl2 2.5 mm, MgSO4 1.2 mm, NaHCO3 25 mm, KH2PO4 1.2 mm, 11.7 mm D- N G -nitro-l-arginine methyl ester L-NAME N-acetyl-1-tryptophan 3,5-bis (trifuluorometyl) benzyl ester L-732,138 Sigma-Aldrich (St Louis ) 7
in vivo α- α- 50 mg/kg α- 40 mg/kg 5 7 mg/kg/h α- 20 25 mg/kg/h 40 mg/kg 7 14 mg/kg 1.2 g/kg In vivo Homeothermic Blanket Systems (Harvard Holliston ) 36 37 C 1 mm 2.4 mm 1.5 mm 5 mm 8
AD Instruments Bella Vista NEW Power Lab System AD Instruments 30 15 (mmhg) 200 mg/kg 9
Rodent Ventilator Model 683 Harvard Bioscience, Boston, Capsaicin Tsuda et al., 2000; Yamashita et al., 2008 10% 10% Tween80 50mg/kg 2 8 9 0.01% in vitro 1.0 cm 10
35 10 ml 95% O2 5% CO2 T7-8-240 ORIENTEC AC STRAIN AMPLIFIER AS1202 NEC Power Lab AD Instruments 1.0 g 30 Model SEN-3201 10 500 µ 1 80 V 100 µ 80 V 1 20 Hz 5 5 D- L NAME L-732,138 500 1000 11
standard deviation SD Dunnet s P 0.05 12
In vivo (mmhg) 13
35 95% O2 5% CO2 10 ml Power Lab 14
in vivo Neuhuber et al., 2006; Wörl and Neuhuber, 2005 Furness, 2006; Clouse and Diamant, 2006 Andrew, 1956; Clouse and Diamant, 2006; Cunningham and Sawchenko, 1990; Goyal and Chaudhury, 2008; Jean, 2001; Lu and Bieger, 1998; Neuhuber et al., 2006 Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2006; Shiina et al., 2012 NO Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2006; Shiina et al., 2012 NO 15
Izumi et al., 2003; Shiina et al., 2006 co-innervation Neuhuber et al., 2006; Wörl and Neuhuber, 2005 Holzer, 1988; Holzer, 2004; Geppetti and Trevisani, 2004; Sasamura and Kuraishi, 1999; Szallasi and Blumberg, 1999; Szolcsanyi and Bartho, 2001; Tominaga and Tominaga, 2005 in vivo in vivo Lu and Bieger, 1998 Sengupta, 2001 Lu and Bieger, 1998; Sang and Goyal, 2001 Satchell, 1984 16
(Bogeski et al., 2005; Shimizu et al., 2006) in vivo 17
in vitro NO NO 18
0 mmhg 4 mmhg - n = 4 n = 4 8 mmhg - 8 mmhg 8 mmhg 19
2 mmhg 4 mmhg 4 mmhg 8 mmhg 4 mmhg 8 mmhg 20
in vivo mmhg ml mmhg 0 1 mmhg 4 mmhg 21
In vivo 4 mmhg 22
8 mmhg mmhg ml mmhg 23
2 4 8 mmhg in vivo mmhg ml mmhg c 24
2 4 8 mmhg in vivo a b µl c mmhg SD (n = 6) P < 0.05 25
8 mmhg a b c d 2 4 8 mmhg in vivo a mmhg b SD (n = 6) P < 0.05 26
in vivo in vivo Clouse and Diamant, 2006 Lu and Bieger, 1998 Clouse and Diamant, 2006; Bieger and Neuhuber 2006; Lu and Bieger, 1998 NMDA GABA Broussard et al., 1996; Broussard et al., 1994 27
Hashimo and Bieger, 1989; Wang and Bieger, 1991 NMDA GABA in vivo 4 mmhg 6 mmhg Satchell, 1984; Yu et al., 2005 Loomis et al., 1997 2 4 8 mmhg in vivo 28
in vivo 29
in vivo TRPV1 ; Izumi et al., 2003; Shiina et al., 2006 In vivo 30
in vivo 4 mmhg 2 mmhg 31
3 2 mmhg 32
8 mmhg mmhg ml mmhg 33
2 4 8 mmhg in vivo a µl mmhg SD n = 6 n = 5 P < 0.05 34
0 8 mmhg SD n = 3 n = 3 35
a 8 mmhg 2 4 8 mmhg in vivo b mmhg SD n = 6 n = 5 P < 0.05 36
in vivo mmhg 0 2 4 mmhg 4 mmhg 2 mmhg 37
in vivo Spencer et al., 2008; Yu et al., 2005 Intraganglionic laminar endings IGLE Berthoud et al., 1997a; Phillips and Powley, 2000; Sengupta, 2000; Zagorodnyuk and Brookes, 2000 Berthoud et al., 1997b; Patterson et al., 2003 38
Andrew, 1956; Clouse and Diamant, 2006; Cunningham and Sawchenko, 1990; Goyal and Chaudhury, 2008; Jean, 2001; Lu and Bieger, 1998; Neuhuber et al., 2006 Spencer et al., 2008; Yu et al., 2005 Banik and Brennan, 2009; Rong et al., 2004 NO NO Page et al., 2009 NO Shiina et al., 2013; Shiina et al., 2006 NO n-nos 2 Masliukov et al., 2015 39
n-nos NO NO Berthoud et al., 1997b; Shiina et al., 2006 in vivo in vivo 40
41
in vivo in vivo Banik and Brennan, 2009; Rong et al., 2004 NO 42
NO ; Boudaka et al., 2007; Izumi et al., 2003; Shiina et al., 2013; Shiina et al., 2012; Shiina et al., 2006 NO in vitro 43
In vitro 30 µm NO L-NAME 200 µm NK1 L-732,138 2 µm 4.27 ± 0.87 g (n = 5) 4.24 ± 44
0.96 g (n = 3) d- d- d- b c d 45
100 µ 80 V 30 µm SD n = 3 n = 3 P < 0.05 46
NO NK1 100 µ 80 V 30 µm NO L-NAME 200 µm NK1 L-732,138 2 µm 30 µm 47
a 100 µ 80 V 100% SD n = 4 n = 4 48
10 100 µ 80 V 100% SD n = 4 n = 4 49
100 µ 80 V 5 1~50 Hz 50
D- a D- 0.5 5 µm 100 µ 80 V D- 0.5 5 µm 100% SD n = 4 n = 4 51
a 100 µ 80 V c d, SD n = 5 n = 3 52
d- 53
d- Jonsson et al., 2009 d- Ca 2+ Nogueira and Hogan, 2010 c Aizawa et al., 2011; De Groat et al., 1982; Yu et al., 2009 in vitro 54
55
in vitro Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2012; Shiina et al., 2006 NO NO NO Neuhuber et al., 2006; Wörl and Neuhuber 2005 in vivo Neuhuber et al., 2006; Wörl and Neuhuber 2005 Furness, 2006; Hansen, 2003; 56
Leonard et al., 2006; Olsson and Holmgren, 2011 Furness, 2006; Hansen, 2003; Leonard et al., 2006; Olsson and Holmgren, 2011 Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2012; Shiina et al., 2006 in vivo Boudaka et al., 2007; Boudaka et al., 2009; Izumi et al., 2003; Shiina et al., 2012; Shiina et al., 2006 in vivo in vitro in vivo in vivo in vitro 57
in vivo > 30 mmhg Spencer et al., 2008; Yu et al., 2005 8 mmhg 58
59
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