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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.(DoctoralDegree) 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。
2
3
4
7
1 in vivo
15
19
27
2
30
31
38
3
42
44
53
56
59
60
3
SD standard deviation
L-NAME NG-nitro-L-arginine methyl ester
TRPV1 transient receptor potential cation channel, subfamily V, member 1
NO nitric oxide
4
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
5
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
6
7
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- NG-nitro-L-arginine methyl ester L-NAME
N-acetyl-1-tryptophan 3,5-bis (trifuluorometyl) benzyl ester L-732,138
Sigma-Aldrich (St Louis )
8
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
9
AD Instruments Bella Vista NEW
Power Lab System AD Instruments
30
15
(mmHg)
200 mg/kg
10
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
11
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
12
standard deviation SD
Dunnet’s
P 0.05
13
In vivo
(mmHg)
14
35 95% O2 5% CO2 10 mL
Power Lab
15
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
16
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
17
(Bogeski et al., 2005; Shimizu et al., 2006)
in vivo
18
in vitro
NO
NO
19
0 mmHg
4 mmHg
- n = 4
n = 4 8 mmHg
-
8 mmHg
8 mmHg
20
2 mmHg
4 mmHg
4 mmHg 8 mmHg
4
mmHg 8 mmHg
21
in vivo
mmHg mL mmHg
0 1 mmHg 4 mmHg
22
In vivo
4 mmHg
23
8 mmHg
mmHg mL mmHg
24
2 4 8 mmHg in vivo
mmHg mL mmHg
c
25
2 4 8 mmHg in vivo
a b µL c
mmHg SD (n = 6) P <
0.05
26
8 mmHg
a b
c d 2
4 8 mmHg in vivo
a mmHg b
SD (n = 6) P
< 0.05
27
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
28
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
29
in vivo
30
in vivo
TRPV1
; Izumi et al., 2003; Shiina et al., 2006
In vivo
31
in vivo
4 mmHg
2 mmHg
32
3
2
mmHg
33
8 mmHg
mmHg mL mmHg
34
2 4 8 mmHg
in vivo
a
µL mmHg
SD n = 6 n = 5 P < 0.05
35
0 8 mmHg
SD
n = 3 n = 3
36
a 8 mmHg
2 4 8 mmHg
in vivo
b mmHg
SD n = 6
n = 5 P < 0.05
37
in vivo mmHg
0 2 4 mmHg
4 mmHg 2
mmHg
38
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
39
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
40
n-NOS
NO
NO
Berthoud et al., 1997b; Shiina et al., 2006
in vivo
in vivo
41
42
in vivo
in vivo
Banik
and Brennan, 2009; Rong et al., 2004 NO
43
NO ; Boudaka et al., 2007; Izumi et al., 2003; Shiina et al.,
2013; Shiina et al., 2012; Shiina et al., 2006
NO
in vitro
44
In vitro
30 µM
NO
L-NAME 200 µM NK1 L-732,138
2 µM
4.27 ± 0.87 g (n = 5) 4.24 ±
45
0.96 g (n = 3)
d-
d-
d-
b c d
46
100 µ 80 V
30 µM
SD n = 3 n = 3 P < 0.05
47
NO
NK1
100 µ
80 V
30 µM NO L-NAME 200 µM
NK1 L-732,138 2 µM30 µM
48
a
100 µ
80 V
100%
SD n = 4 n = 4
49
10 100 µ 80 V
100%
SD n = 4
n = 4
50
100 µ
80 V 5 1~50 Hz
51
D-
a
D- 0.5 5 µM
100 µ 80 V
D- 0.5 5 µM
100% SD
n = 4 n = 4
52
a
100 µ 80 V c d,
’ ’ ’ SD
n = 5 n = 3
53
d-
54
d-
Jonsson et al., 2009 d-
Ca2+ Nogueira and Hogan, 2010
c
Aizawa et al., 2011; De Groat et al., 1982; Yu et al., 2009
in vitro
55
56
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;
57
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
58
in vivo
> 30 mmHg
Spencer et al., 2008; Yu et al., 2005
8 mmHg
59
60
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