Up-regulation of H2 receptor and adenylate cyclase in rabbit parietal cells during prolonged treatment with H2-receptor antagonists

Intragastric hyperacidity occurs after abrupt withdrawal of histamine H(2)-receptor antagonists, and the prolonged administration of these agents induces tachyphylaxis of the inhibitory effects on gastric acid secretion. We examined the effect Of the prolonged administration of H(2)-receptor antagonistson the H(2)-receptor signaling system in parietal cells isolated from rabbits that had received H(2)-receptor antagonists for 14 days. [(125)I]aminopotentidine (APT) binding sites to H(2) receptors in parietal cell membranes were increased without any significant change in the affinity for [(125)I]APT. The expression of Gsa, guanosine triphosphate (GTP)-binding protein coupled to H(2) receptor, was slightly increased. Basal as well as GTP- or histamine-stimulated cAMP production was increased, but no significant change was observed in the presence of an H(2)-receptor antagonist. The up-regulation of the H(2) receptor and adenylate cyclase appeared to cause hypersecretion of acid after withdrawal of H(2) receptor blockade.