Inhibition of pepsinogen secretion in isolated gastric glands by amphotericin B is secretagogue specific.
Pepsinogen secretion from isolated gastric glands, stimulated by 8-bromoadenosine 3',5'-cyclic monophosphate (8BrcAMP), forskolin, or cholecystokinin octapeptide, was inhibited by the presence of amphotericin B in the incubation medium. However, amphotericin had no effect, or only a slight effect (less than 10% inhibition), on pepsinogen secretion stimulated by crude secretin. Incubation of glands with either of the mitochondrial inhibitors, rotenone or carbonyl cyanide m-chlorophenylhydrazone, reduced pepsinogen secretory responses both to 8BrcAMP and to crude secretin. This suggests that amphotericin inhibition, which is secretagogue specific, was not the result of a general metabolic inhibition. Amphotericin caused an increase in sodium and chloride content and a decrease in potassium content of glands. Experiments in which the medium content of either sodium, potassium, or chloride was varied, suggested that part of the amphotericin inhibition could be attributed to a rise in intracellular chloride content. Results did not support the involvement of changes in intracellular sodium or potassium content in the inhibitory mechanism of amphotericin. It was concluded that amphotericin caused a rapid and secretagogue-specific inhibition of pepsinogen secretion in isolated gastric glands, and that the mechanism of inhibition may, to some extent, involve changes in intracellular chloride content.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D004734:Energy Metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D010435:Pepsinogens / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012844:Sincalide / Q000494:pharmacology
D002712:Chlorides; D004224:Diterpenes; D007476:Ionophores; D010435:Pepsinogens; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000666:Amphotericin B; D012844:Sincalide; D011188:Potassium