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 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 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 relaxations of the stomach. These were unaffected by tetrodotoxin (2 microM) or N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM). 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 neurotransmitter of vagally induced gastric relaxation in the guinea pig.
Desai
K M
KM
Department of Pharmacology, Boyer Center for Molecular Medicine, Yale University, New Haven, CT 06536-0812.
Warner
T D
TD
Bishop
A E
AE
Polak
J M
JM
Vane
J R
JR
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005748:Gastric Fundus / Q000187:drug effects / Q000201:enzymology / Q000294:innervation; D006168:Guinea Pigs; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000201:enzymology / Q000294:innervation / Q000502:physiology*; D009197:Myenteric Plexus / Q000187:drug effects / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester; D018377:Neurotransmitter Agents / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*
D018377:Neurotransmitter Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester