title: Phorbol ester-mediated desensitization of histamine H1 receptors on a cultured smooth muscle cell line.
abstract: The present study was undertaken in order to examine the effect of protein kinase C (PKC) on histamine H1 receptors (H1R) present on the smooth muscle cell line, DDT1MF-2. [3H]-pyrilamine binding revealed that specific [3H]-pyrilamine binding sites were reduced by pretreatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of PKC, but not the Kd. The TPA analogue, 4 alpha phorbol 12,13-didecanoate, which does not activate PKC, failed to induce down-regulation of H1R. TPA-induced down-regulation of H1R was inhibited by pretreatment with 1-(5-Isoquinilinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), a PKC inhibitor, in a dose dependent manner. The H-7 analogue, H-8, which is a less potent inhibitor of PKC, but a potent inhibitor of cyclic nucleotide dependent protein kinase, had no effect on H1R. Moreover, treatment with TPA inhibited histamine-induced increases in [Ca2+]i in cells loaded with the fluorescent indicator, indo-1. These data suggest that H1R in DDT1MF-2 cells are functionally regulated by PKC.
authors.affiliation: Howard Hughes Medical Institute, University of California Medical Center, San Francisco 94143.
authors.forename: M
authors.initials: M
authors.lastname: Mitsuhashi
authors.forename: D G
authors.initials: DG
authors.lastname: Payan
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D007211:Indoles / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011738:Pyrilamine / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007211:Indoles; D007546:Isoquinolines; D010879:Piperazines; D011969:Receptors, Histamine H1; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D011738:Pyrilamine; C048960:indo-1; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium