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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