Mediators of nicotine‐induced relaxations of the rat gastric fundus

1. Relaxations of strips of rat gastric fundus were elicited with nicotine (100 μmol/L), nitric oxide (NO; 30 μmol/L), sodium nitroprusside (SNP; 100 nmol/L) and vasoactive intestinal polypeptide (VIP; 1 nmol/L). 2. Methylene blue (30 μmol/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. N^G‐nitro‐l‐arginine methyl ester (l‐NAME; 100 μmol/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 μmol/L) or hexamethonium (100 μmol/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.