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.