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

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.