Mediators of nicotine-induced relaxations of the rat gastric fundus.
1. Relaxations of strips of rat gastric fundus were elicited with nicotine (100 mumol/L), nitric oxide (NO; 30 mumol/L), sodium nitroprusside (SNP; 100 nmol/L) and vasoactive intestinal polypeptide (VIP; 1 nmol/L). 2. Methylene blue (30 mumol/L), an inhibitor of soluble guanylate cyclase, reduced relaxations elicited by NO and nicotine, but not those elicited by VIP. 3. Chymotrypsin (1 U/mL) abolished VIP-induced relaxations and reduced nicotine-induced relaxations, but had no effect on SNP-induced relaxations. 4. NG-nitro-L-arginine methyl ester (L-NAME; 100 mumol/L), an inhibitor of NO synthase, reduced relaxations elicited by nicotine, but not those elicited by SNP or VIP. 5. When nicotine-induced relaxations had been reduced by either L-NAME or chymotrypsin, the addition of the other agent produced a greater reduction. However, the relaxations were not abolished. 6. Nicotine-induced relaxations were abolished by tetrodotoxin (1 mumol/L) or hexamethonium (100 mumol/L), indicating that they were due to activation of neuronal nicotinic receptors. Their reduction by methylene blue and L-NAME indicates that an NO-like mediator was involved. Their reduction by chymotrypsin indicates that a VIP-like peptide was involved. However, since they were not abolished by a combination of L-NAME and chymotrypsin, it appears that at least one more as yet unidentified mediator may be involved.
McLaren
A
A
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Li
C G
CG
Rand
M J
MJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002918:Chymotrypsin / Q000494:pharmacology; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D009599:Nitroprusside; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D009538:Nicotine; D001120:Arginine; D002918:Chymotrypsin; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester