Desensitization by histamine of H2 receptor activity in HGT-1 human cancerous gastric cells

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Abstract
Histamine produced a time-dependent (half-life: 20 min at 37°C), temperature-dependent (no effect at 20°C) and homologous desensitization of histamine H2 receptor activity (H2 R) in HGT-1 cells. Maximal and half-maximal desensitization were respectively observed at 10−5 and 2×10−7 M histamine. Decline of responsiveness in intact cells was related to a remarkable loss in histamine efficacy (from 15- to 2-fold stimulation in control and treated cells). The affinity of the H2R for histamine (EC50=10−5 M) did not change during desensitization. Paradoxically, histamine treatment is associated with increased [3H] histamine binding capacity in intact HGT-1 cells, and no change in H2 receptor antagonist binding ([3H]-tiodine and [3H]-SKF 93479). Desensitization process was preferentially mimicked by H2 receptor agonists (impromidine > histamine > AET > PEA) and preferentially reversed by simultaneous addition of H2 receptor antagonists (cimetidine > DPH). We suggest that the desensitization of H2R activity by histamine presented here may be involved in the pathophysiological regulation and pharmacological control of gastric cell function in man.