REGULATION OF HISTAMINE H1 RECEPTOR-MEDIATED PHOSPHOINOSITIDE HYDROLYSIS BY HISTAMINE AND PHORBOL ESTERS IN DDT1 MF-2 CELLS

The regulation of histamine-stimulated phosphoinositide turnover by histamine and phorbol esters was examined in intact DDT1 MF-2 cells grown in suspension culture. Histamine increased the incorporation of P-32 into phosphatidylinositol (PI) in these cells, and this stimulation was inhibited by the H-1 antagonist diphenhydramine but not by the H-2 antagonist cimetidine. Pretreatment of cells with histamine or with phorbol 12-myristate 13-acetate (PMA) or other activators of protein kinase C induced a marked decrease in the subsequent stimulation by histamine. PMA, but not histamine, also decreased the ability of epinephrine to stimulate PI labelling through alpha-1-adrenoceptors. Thus, histamine appears to induce homologous desensitization of histamine H-1 receptor-mediated PI turnover, whereas direct activation of protein kinase C in the absence of receptor occupancy by agonist induces nonspecific heterologous desensitization of both histamine H-1- and alpha-1-adrenoceptor-mediated responses.