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 H2-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 H2-receptor antagonists on the H2-receptor signaling system in parietal cells isolated from rabbits that had received H2-receptor antagonists for 14 days. [125I]aminopotentidine (APT) binding sites to H2 receptors in parietal cell membranes were increased without any significant change in the affinity for [125I]APT. The expression of Gs(alpha), guanosine triphosphate (GTP)-binding protein coupled to H2 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 H2-receptor antagonist. The up-regulation of the H2 receptor and adenylate cyclase appeared to cause hypersecretion of acid after withdrawal of H2-receptor blockade.
Takeuchi
K
K
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
Kajimura
M
M
Kodaira
M
M
Lin
S
S
Hanai
H
H
Kaneko
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D011817:Rabbits; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D006146:Guanidines; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011970:Receptors, Histamine H2; C103275:aminopotentidine; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases