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

Year 2002, Volume: 15 Issue: 1, 7 - 14, 03.12.2016

Ece İskender Hülya Cabadak Ahmet Akıcı Zafer Gören Atila Karaalp Nefise Ulusoy Beki Kan Esam El-fakahany Şule Oktay

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 (1mmol/l) and scopolamine (108-
106 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 (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 subtype(s) involved in this interaction remains to be elucidated.
Key Words: cGMP, NO, Guinea-pig,
gallbladder, L-NAME, L-NMMA

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