Evidence for a direct action of acetylcholine on the gastric oxyntic cell of the amphibian.
The possibility of a direct action of acetylcholine (ACh) on the oxyntic cell not mediated by histamine release was studied in resting isolated gastric mucosae. H+ secretion and histamine release, and their relationship, were studied under ACh stimulation and other conditions. ACh released histamine from mucosal stores and stimulated H+ secretion. H2-receptor blocker cimetidine largely inhibited ACh-induced stimulation of H+ transport but not histamine release. Atropine inhibited the cholinergic response in both histamine release and H+ secretion. The dose-response curves to ACh showed nonparallel increases in H+ secretion and histamine release. When dose-response curves to exogenous and endogenous histamine (released by ACh) were compared, it was found that ACh increased Vmax for endogenous histamine. Comparison of the effects of ACh with other experimental conditions such as tetragastrin treatment, K+ depolarization, or Na+-free nutrient solution showed that the amount of histamine released by ACh was insufficient to explain the observed rates of secretion. Stimulation by ACh was faster, greater, and more transitory compared with that by histamine. In mucosae maximally stimulated by histamine, ACh induced a further increase in H+ secretion. In the presence of cimetidine, potentiation between ACh and dibutyryl cAMP or isobutyl-methylxanthine was found. The results are consistent with ACh having a dual action on oxyntic and histamine-releasing cells. The action of ACh on the oxyntic cell would potentiate the effect of released histamine. It is suggested that ACh and released histamine act on the oxyntic cell through different second messengers, resulting in the potentiated response.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D007700:Kinetics; D011892:Rana catesbeiana
D001626:Bethanechol Compounds; D018723:Bethanechol; D003994:Bucladesine; D001285:Atropine; D002927:Cimetidine; D000242:Cyclic AMP; D000109:Acetylcholine; D015056:1-Methyl-3-isobutylxanthine