C A R B A C H O L I N D U C E S N I T R I C O X I D E G E N E R A T I O N I N G U I N E A - P I G G A L L B L A D D E R

Authors : Ece İSKENDER, Hülya CABADAK, Ahmet AKICI, Zafer GÖREN, Atila KARAALP, Nefise ULUSOY, Beki KAN, Esam ELFAKAHANY, Şule OKTAY

Pages : 7-14

View : 16 | Download : 3

Publication Date : 2016-12-03

Article Type : Research Paper

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 insert ignore into journalissuearticles values(NO); which activates soluble guanylate cyclase to increase cyclic GMP insert ignore into journalissuearticles values(cGMP); levels in the target cells may be involved in these processes. This study was designed to investigate whether muscarinic receptor stimulation via carbachol insert ignore into journalissuearticles values(CCh); induces NO-mediated cGMP synthesis in guinea-pig gallbladder. Methods: cGMP levels were measured via radioimmunoassay in gallbladder slices incubated with carbachol insert ignore into journalissuearticles values(CCh); insert ignore into journalissuearticles values(10 6-10 3 mol/l); in the presence and absence of NO synthase insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(1mmol/l); and scopolamine insert ignore into journalissuearticles values(108- 106 mol/l);. In contraction experiments, L-NAME insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(3x10-4 mol/l); induced a slight, but significant contraction insert ignore into journalissuearticles values(6.3+1.9 % of carbachol insert ignore into journalissuearticles values(106 mol/l);-induced response);. When carbachol was added to the bath after L-NMMAinduced 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 subtypeinsert ignore into journalissuearticles values(s); involved in this interaction remains to be elucidated. Key Words: cGMP, NO, Guinea-pig, gallbladder, L-NAME, L-NMMA
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