Selective disappearance of histamine H2-receptor activity in the human gastric cancer cell line HGT-1 after short-term or chronic treatment by histamine or its H2-antagonists.

Homologous loss of histamine H2-receptor activity (cAMP generation) was observed after short-term (10-20 min) or chronic treatment (6 days) of cultured HGT-1 cells with histamine (desensitization) or the H2-receptor antagonist SKF 93479. This inactivation process was not observed when HGT-1 cells were exposed to the classical H2-antihistamine cimetidine. The data show: (1) that the compound SKF 93479 has a very prolonged inhibitory action on histamine receptor activity, suggesting an irreversible interaction between the antagonist and the receptor; (2) that cimetidine is a reversible H2-receptor antagonist which can be removed without changing the the efficacy and the potency of histamine on gastric cells; (3) that the H2-receptor antagonists cimetidine and SKF 93479 specifically block histamine H2-receptor activity in HGT-1 cells since cAMP generation induced by other hormones such as vasoactive intestinal peptide (VIP), glucagon or gastric inhibitory peptide (GIP) was unchanged after treatment; (4) the first evidence for time-dependent (half-life: 20 min) desensitization of gastric H2-receptors.