The role of protein kinase A and protein kinase C in prostanoid IP receptor desensitization in NG108-15 cells.
Pretreatment of NG108-15 cells for 1 h with 1 microM phorbol 12-myristate,13-acetate produced no significant effect on the subsequent stimulation of adenylate cyclase activity by the IP receptor agonist, iloprost, the adenosine A2 receptor agonist, N-ethylcarboxamidoadenosine (NECA), or sodium fluoride, suggesting that protein kinase C activation does not produce desensitization in this system. Pretreatment of cells with 10 microM iloprost or forskolin for 17 h produced a decrease in the specific binding of [3H]iloprost, consistent with a decrease in IP receptor number. Iloprost pretreatment produced a decrease in responses to iloprost, NECA and sodium fluoride, whereas forskolin pretreatment produced a decrease in subsequent responsiveness to iloprost and NECA, but the response to sodium fluoride remained unaffected. The desensitization produced by forskolin could be completely inhibited by the inhibitor of protein kinase A and protein kinase C, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), but H7 had no effect on the desensitization produced by iloprost.
Krane
A
A
Department of Pharmacology, Medical School, University of Birmingham, UK.
Malkhandi
J
J
Mercy
L
L
Keen
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006822:Hybrid Cells; D016285:Iloprost / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011982:Receptors, Prostaglandin / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007546:Isoquinolines; D010879:Piperazines; D011982:Receptors, Prostaglandin; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D016285:Iloprost; D013755:Tetradecanoylphorbol Acetate