Mechanism of the effect of gizzerosine, an inducer of gizzard erosion in chicks, on acid secretion by isolated mucosal cells of chicken proventriculus.

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Mucosal cells of the chicken proventriculus were isolated by a collagenase perfusion method and O_2 uptake by the isolated cells was measured as an index of the activity of gastric acid secretion. Oxygen consumption was enhanced by histamine; this effect was augmented by the coexistence of isobutylmethylxanthine, an inhibitor of cyclic adenosine 5'-monophosphate (AMP) phosphodiesterase, and suppressed by imidazole, an activator of the enzyme. The action of histamine was inhibited by cimetidine, an antagonist of the histamine H_2 receptor. These results indicate that the isolated cells retained the capacity to take up O_2 responding to histamine via the H_2 receptor and probably the cyclic AMP level. Gizzerosine also stimulated O_2 consumption by the isolated cells. The effect of gizzerosine was cancelled by cimetidine, suggestig that the mechanism by which gizzerosine acts on the mucosal cells is similar to that of histamine action.Gizzerosine increased intracellular cyclic AMP level, reaching a plateau within 30 min. Similar maxima of cyclic AMP level was observed in the presence of histamine of gizzerosine. However, the potency of gizzerosine was approximately a thousand fold higher than that of histamine. The action o gizzerosine was depressed by cimetidine but not by pyrilamine, a histamine H_1-receptor antagonist, indicating that gizzerosine is a very strong histamine H_2-receptor agonist.