Irreversible and specific inactivation by AH 22216 of histamine H2 receptors in the human gastric cancer cell line HGT-1.
We compared the interaction of AH 22216 (a new histamine H2 receptor antagonist) and cimetidine on the receptor-cAMP systems sensitive to histamine and to Vasoactive Intestinal Peptide (VIP) in the human gastric cancer cell line HGT-1. When added simultaneously with histamine (10(-4) M), the potency of AH 22216 is similar to that of cimetidine (IC50 = 4-6.6 X 10(-6) M, respectively). Schild plot analysis indicated a non-competitive inhibition by AH 22216 (pA2 = 6.22, slope = 1.4 +/- 0.03). Preincubations of AH 22216 (10 min, 10(-5) M) with HGT-1 cells (even after a washout period) resulted in a complete and persistent (60 min) inactivation of the subsequent histamine effect, without changing the kinetics of the VIP-induced stimulation in the system. Under these conditions, the potency of AH 22216 increased from 6.6 to 0.7 X 10(-6) M. This inactivation was not observed with cimetidine. The data indicate that AH 22216 is an irreversible and specific inhibitor of the gastric histamine H2 receptor.
D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013270:Stomach / Q000502:physiology*; D014230:Triazoles; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D010880:Piperidines; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D014230:Triazoles; D014660:Vasoactive Intestinal Peptide; D006632:Histamine; C038304:lamtidine; D000242:Cyclic AMP