Carbachol induces nitric oxide generation in guinea-pig gallbladder

Ece Iskender; Hülya Cabadak; Ahmet Akici; M. Zafer Gören; Atila Karaalp; Nefise B. Ulusoy; Beki Kan; Esam E. El-Fakahany; Şule Oktay

Carbachol induces nitric oxide generation in guinea-pig gallbladder

Ece Iskender, Hülya Cabadak, Ahmet Akici, M. Zafer Gören, Atila Karaalp, Nefise B. Ulusoy, Beki Kan, Esam E. El-Fakahany, Şule Oktay

Experimental and Clinical Pharmacology

Research output: Contribution to journal › Article › peer-review

Abstract

Objective: Acetylcholine is one of the major contractile transmitters in gallbladder; whereas, it is also innervated by non-adrenergic noncholinergic nerves which mediate relaxation. It was postulated that nitric oxide (NO) which activates soluble guanylate cyclase to increase cyclic GMP (cGMP) levels in the target cells may be involved in these processes. This study was designed to investigate whether muscarinic receptor stimulation via carbachol (CCh) induces NO-mediated cGMP synthesis in guinea-pig gallbladder. Methods: cGMP levels were measured via radioimmunoassay in gallbladder slices incubated with carbachol (CCh) (10^-6-10^-3 mol/l) in the presence and absence of NO synthase (NOS) inhibitor L-NAME or muscarinic antagonist scopolamine. The effect of L-NAME and another NOS inhibitor L-NMMA on carbachol-induced contractions were also investigated in an in vitro organ bath. Results: Carbachol stimulated cGMP formation in guinea-pig gallbladder slices significantly. CCh-induced cGMP formation was abolished by both L-NAME (1 mmol/l) and scopolamine (10^-8- 10^-6 mol/l). In contraction experiments, L-NAME (3x10^-4 mol/l) did not produce any change in the resting tension of the strips and the concentration-response curves to carbachol, whereas L-NMMA (3x10^-4 mol/l) induced a slight, but significant contraction (6.3±1.9 % of carbachol (10^-6 mol/l)-induced response). When carbachol was added to the bath after L-NMMA-induced increase in tension reached its maximum, the amplitude of the contractile response at the end was 108.0±4.0 % of the control. Conclusion: Therefore, it may be concluded that muscarinic receptor activation by carbachol stimulates NO production in guinea-pig gallbladder and the subsequent increase in cGMP counteracts with carbachol-induced contractions. However, it seems likely that an intact enteric nervous system is required for such an interaction to be prominent. The muscarinic receptor subtype(s) involved in this interaction remains to be elucidated.

Original language	English (US)
Pages (from-to)	7-14
Number of pages	8
Journal	Marmara Medical Journal
Volume	15
Issue number	1
State	Published - Jan 2002

Keywords

CGMP
Gallbladder
Guinea-pig
L-NAME
L-NMMA
NO

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title = "Carbachol induces nitric oxide generation in guinea-pig gallbladder",

abstract = "Objective: Acetylcholine is one of the major contractile transmitters in gallbladder; whereas, it is also innervated by non-adrenergic noncholinergic nerves which mediate relaxation. It was postulated that nitric oxide (NO) which activates soluble guanylate cyclase to increase cyclic GMP (cGMP) levels in the target cells may be involved in these processes. This study was designed to investigate whether muscarinic receptor stimulation via carbachol (CCh) induces NO-mediated cGMP synthesis in guinea-pig gallbladder. Methods: cGMP levels were measured via radioimmunoassay in gallbladder slices incubated with carbachol (CCh) (10-6-10-3 mol/l) in the presence and absence of NO synthase (NOS) inhibitor L-NAME or muscarinic antagonist scopolamine. The effect of L-NAME and another NOS inhibitor L-NMMA on carbachol-induced contractions were also investigated in an in vitro organ bath. Results: Carbachol stimulated cGMP formation in guinea-pig gallbladder slices significantly. CCh-induced cGMP formation was abolished by both L-NAME (1 mmol/l) and scopolamine (10-8- 10-6 mol/l). In contraction experiments, L-NAME (3x10-4 mol/l) did not produce any change in the resting tension of the strips and the concentration-response curves to carbachol, whereas L-NMMA (3x10-4 mol/l) induced a slight, but significant contraction (6.3±1.9 % of carbachol (10-6 mol/l)-induced response). When carbachol was added to the bath after L-NMMA-induced increase in tension reached its maximum, the amplitude of the contractile response at the end was 108.0±4.0 % of the control. Conclusion: Therefore, it may be concluded that muscarinic receptor activation by carbachol stimulates NO production in guinea-pig gallbladder and the subsequent increase in cGMP counteracts with carbachol-induced contractions. However, it seems likely that an intact enteric nervous system is required for such an interaction to be prominent. The muscarinic receptor subtype(s) involved in this interaction remains to be elucidated.",

keywords = "CGMP, Gallbladder, Guinea-pig, L-NAME, L-NMMA, NO",

author = "Ece Iskender and H{\"u}lya Cabadak and Ahmet Akici and {Zafer G{\"o}ren}, M. and Atila Karaalp and Ulusoy, {Nefise B.} and Beki Kan and El-Fakahany, {Esam E.} and {\c S}ule Oktay",

year = "2002",

month = jan,

language = "English (US)",

volume = "15",

pages = "7--14",

journal = "Marmara Medical Journal",

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number = "1",

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TY - JOUR

T1 - Carbachol induces nitric oxide generation in guinea-pig gallbladder

AU - Iskender, Ece

AU - Cabadak, Hülya

AU - Akici, Ahmet

AU - Zafer Gören, M.

AU - Karaalp, Atila

AU - Ulusoy, Nefise B.

AU - Kan, Beki

AU - El-Fakahany, Esam E.

AU - Oktay, Şule

PY - 2002/1

Y1 - 2002/1

N2 - Objective: Acetylcholine is one of the major contractile transmitters in gallbladder; whereas, it is also innervated by non-adrenergic noncholinergic nerves which mediate relaxation. It was postulated that nitric oxide (NO) which activates soluble guanylate cyclase to increase cyclic GMP (cGMP) levels in the target cells may be involved in these processes. This study was designed to investigate whether muscarinic receptor stimulation via carbachol (CCh) induces NO-mediated cGMP synthesis in guinea-pig gallbladder. Methods: cGMP levels were measured via radioimmunoassay in gallbladder slices incubated with carbachol (CCh) (10-6-10-3 mol/l) in the presence and absence of NO synthase (NOS) inhibitor L-NAME or muscarinic antagonist scopolamine. The effect of L-NAME and another NOS inhibitor L-NMMA on carbachol-induced contractions were also investigated in an in vitro organ bath. Results: Carbachol stimulated cGMP formation in guinea-pig gallbladder slices significantly. CCh-induced cGMP formation was abolished by both L-NAME (1 mmol/l) and scopolamine (10-8- 10-6 mol/l). In contraction experiments, L-NAME (3x10-4 mol/l) did not produce any change in the resting tension of the strips and the concentration-response curves to carbachol, whereas L-NMMA (3x10-4 mol/l) induced a slight, but significant contraction (6.3±1.9 % of carbachol (10-6 mol/l)-induced response). When carbachol was added to the bath after L-NMMA-induced increase in tension reached its maximum, the amplitude of the contractile response at the end was 108.0±4.0 % of the control. Conclusion: Therefore, it may be concluded that muscarinic receptor activation by carbachol stimulates NO production in guinea-pig gallbladder and the subsequent increase in cGMP counteracts with carbachol-induced contractions. However, it seems likely that an intact enteric nervous system is required for such an interaction to be prominent. The muscarinic receptor subtype(s) involved in this interaction remains to be elucidated.

AB - Objective: Acetylcholine is one of the major contractile transmitters in gallbladder; whereas, it is also innervated by non-adrenergic noncholinergic nerves which mediate relaxation. It was postulated that nitric oxide (NO) which activates soluble guanylate cyclase to increase cyclic GMP (cGMP) levels in the target cells may be involved in these processes. This study was designed to investigate whether muscarinic receptor stimulation via carbachol (CCh) induces NO-mediated cGMP synthesis in guinea-pig gallbladder. Methods: cGMP levels were measured via radioimmunoassay in gallbladder slices incubated with carbachol (CCh) (10-6-10-3 mol/l) in the presence and absence of NO synthase (NOS) inhibitor L-NAME or muscarinic antagonist scopolamine. The effect of L-NAME and another NOS inhibitor L-NMMA on carbachol-induced contractions were also investigated in an in vitro organ bath. Results: Carbachol stimulated cGMP formation in guinea-pig gallbladder slices significantly. CCh-induced cGMP formation was abolished by both L-NAME (1 mmol/l) and scopolamine (10-8- 10-6 mol/l). In contraction experiments, L-NAME (3x10-4 mol/l) did not produce any change in the resting tension of the strips and the concentration-response curves to carbachol, whereas L-NMMA (3x10-4 mol/l) induced a slight, but significant contraction (6.3±1.9 % of carbachol (10-6 mol/l)-induced response). When carbachol was added to the bath after L-NMMA-induced increase in tension reached its maximum, the amplitude of the contractile response at the end was 108.0±4.0 % of the control. Conclusion: Therefore, it may be concluded that muscarinic receptor activation by carbachol stimulates NO production in guinea-pig gallbladder and the subsequent increase in cGMP counteracts with carbachol-induced contractions. However, it seems likely that an intact enteric nervous system is required for such an interaction to be prominent. The muscarinic receptor subtype(s) involved in this interaction remains to be elucidated.

KW - CGMP

KW - Gallbladder

KW - Guinea-pig

KW - L-NAME

KW - L-NMMA

KW - NO

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Carbachol induces nitric oxide generation in guinea-pig gallbladder

Abstract

Keywords

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