NITRIC-OXIDE, AND NOT VASOACTIVE-INTESTINAL-PEPTIDE, AS THE MAIN NEUROTRANSMITTER OF VAGALLY INDUCED RELAXATION OF THE GUINEA-PIG STOMACH

1 Nitric oxide synthase (NOS) was localized in the guinea pig stomach by immunocytochemistry. In vitro experiments were carried out on the i solated stomach of the guinea pig to study any possible links between nitric oxide (NO) and vasoactive intestinal peptide (VIP) in mediating relaxations induced by vagal stimulation. 2 NOS was localized to nerv e cell bodies and nerve fibre varicosities of the myenteric plexus in wholemounts of the longitudinal muscle-myenteric plexus of the stomach fundus. The NOS-positive cells had a Dogiel type I morphology charact eristic of motor neurones. 3 The cross-sections of the stomach wall sh owed NOS-positive neurones mainly in the myenteric plexus ganglia and NOS-positive nerve fibre varicosities in the circular muscle layer. 4 Relaxations induced by vagal stimulation were almost completely preven ted by L-NAME with an IC50 value of 5.5 x 10(-6)M. This inhibition was reversed by L-arginine (2 mM). 5 VIP (100 nM) induced reproducible re laxations of the stomach. These were unaffected by tetrodotoxin (2 mu M) or N-omega-nitro-L-arginine methyl ester (L-NAME, 100 mu M). 6 Dese nsitization to the relaxant effect of VIP partially reduced relaxation s induced by vagal stimulation, glyceryl trinitrate or sodium nitropru sside but not noradrenaline. 7 These results show that NO has a neuron al origin in the guinea pig stomach, and support NO, and not VIP, as t he major neurotranmitter of vagally induced gastric relaxation in the guinea pig.