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 32P into phosphatidylinositol (PI) in these cells, and this stimulation was inhibited by the H1 antagonist diphenhydramine but not by the H2 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 H1 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 H1- and alpha 1-adrenoceptor-mediated responses.
Cowlen
M S
MS
Department of Pharmacology, School of Medicine, University of Missouri-Columbia 65212.
Barnes
M R
MR
Toews
M L
ML
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004837:Epinephrine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006868:Hydrolysis; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D011493:Protein Kinase C / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010703:Phorbol Esters; D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; D011969:Receptors, Histamine H1; D006632:Histamine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine