Pharmacological control of the histamine H2 receptor-adenylate cyclase system by famotidine and ranitidine in normal and cancerous human gastric epithelia.

In human fundic glands, famotidine was about 17 times more potent than ranitidine as an inhibitor of histamine - stimulated cAMP generation. This H2-receptor antagonist had no effect on the receptor-adenylate cyclase systems sensitive to PGE2, isoproterenol (beta 2-receptor), VIP and on forskolin-induced activation of the Gs/catalytic units of the membrane-bound enzyme prepared from human fundic glands. In the HGT-1 human gastric cancer cell line, famotidine and ranitidine showed long lasting, irreversible actions probably related to a slow rate of dissociation from the histamine H2-receptor.