Rapid desensitization of the histamine H₂ receptor on the human monocytic cell line U937

Abstract

In the present study we have subjected the histamine H₂ receptor on the monocytic cell line U937 to a thorough pharmacological characterization using a series of selective histamine H₁, H₂ and H₃ receptor agonists and antagonists. Recent reports have demonstrated the existence of a histamine H₂ receptor on HL-60 and HGT-1 cells with a pharmacological profile distinct from the commonly described histamine H₂ receptor. U937 cells, however, seem to express classical histamine H₂ receptors. Histamine and dimaprit dose dependently induce the formation of cAMP, whereas dimaprit's inactive analogues, nordimaprit and homodimaprit, show reduced potencies. Histamine H₁ and H₃ receptor agonists do not show histamine H₂ receptor activity. Various histamine H₂ receptor antagonists are able to block the histamine induced production of cAMP with an antagonistic profile comparable to that observed in the guinea-pig right atrium. Furthermore, endogenous histamine H₂ receptors in U937 cells are found to be susceptible to receptor desensitization, a mechanism which may become apparent under pathophysiological conditions or during drug therapy. A 30-min pre-exposure of U937 cells to histamine (100 μM) results in a 50% attenuation of the production of cAMP to a subsequent application of an agonist. Desensitization of the histamine H₂ receptor in U937 cells is found to be homologous as the β-adrenoceptor mediated response remained unaffected.