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

用胶原酶灌流法分离鸡前胃粘液细胞，测定其摄氧量，作为胃酸分泌活性的指标。氧消耗增加组胺，这种效果是由共存的异丁基甲基黄嘌呤，环腺苷5 '-磷酸（AMP）磷酸二酯酶的抑制剂，并抑制咪唑，该酶的激活剂。组胺H_2受体拮抗剂西咪替丁可抑制组胺的作用。这些结果表明，分离的细胞保留了通过H_2受体和cAMP水平对组胺产生反应的摄取O_2的能力。Gizzerosine也能刺激离体细胞的O_2消耗。Gizzerosine对粘膜细胞的作用机制与组胺作用的机制相似，Gizzerosine可使细胞内cAMP水平升高，在30 min内达到一个平台，在Gizzerosine的组胺存在下也可观察到类似的最大cAMP水平。然而，吉泽罗新的效力比组胺高约一千倍。盐酸西咪替丁可抑制盐酸吉泽罗新的作用，而组胺H_1受体拮抗剂吡拉明则不抑制，表明盐酸吉泽罗新是一种很强的组胺H_2受体激动剂。

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.