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Nitric oxide, and not vasoactive intestinal peptide, as the main neurotransmitter of vagally induced relaxation of the guinea pig stomach
Author(s) -
Desai K.M.,
Warner T.D.,
Bishop A.E.,
Polak J.M.,
Vane J.R.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17124.x
Subject(s) - vasoactive intestinal peptide , neurotransmitter , guinea pig , nitric oxide , endocrinology , medicine , stomach , vasoactive , chemistry , neuropeptide , receptor
1 Nitric oxide synthase (NOS) was localized in the guinea pig stomach by immunocytochemistry. In vitro experiments were carried out on the isolated 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 nerve 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 characteristic of motor neurones. 3 The cross‐sections of the stomach wall showed 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 prevented by 1 ‐NAME with an IC 50 value of 5.5 × 10 −6 m . This inhibition was reversed by L‐arginine (2 μ m ). 5 VIP (100 n m ) induced reproducible relaxations of the stomach. These were unaffected by tet‐rodotoxin (2μ m ) or N W ‐nitro‐L‐arginine methyl ester ( 1 ‐NAME, 100 μ m ). 6 Desensitization to the relaxant effect of VIP partially reduced relaxations induced by vagal stimulation, glyceryl trinitrate or sodium nitroprusside but not noradrenaline. 7 These results show that NO has a neuronal origin in the guinea pig stomach, and support NO, and not VIP, as the major neurotranmitter of vagally induced gastric relaxation in the guinea pig.