Interaction between a phorbol ester and dopamine DA1 receptors on vascular smooth muscle.
The interaction between dopamine DA1 receptors and a phorbol ester was studied to elucidate the role of protein kinase C in the response of this receptor. The in vitro binding of [3H]Sch 23390 to DA1 receptor sites on vascular smooth muscle cells was saturable. The extent of [3H]Sch 23390 binding to phorbol ester-treated cells was increased without any change in the dissociation constant. The production of adenosine 3',5'-cyclic monophosphate (cAMP) in response to DA1 receptor stimulation was enhanced by preincubation of vascular smooth muscle cells with the phorbol ester for 4 h. However, no enhancement was observed when the medium used for preincubation was supplemented with a protein kinase C inhibitor. Direct stimulation of stimulatory guanine nucleotide-binding regulatory protein with 5-guanylylimidodiphosphate and direct stimulation of adenylate cyclase with forskolin produced no significant differences in cyclase levels between phorbol ester-treated and untreated cells. These results suggest that activation of protein kinase C triggers an increase in the membrane expression of DA1 receptors, thereby enhancing receptor-coupled cAMP generation.
First Department of Internal Medicine, Osaka City University Medical School, Japan.
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Yasunari
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Kohno
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Murakawa
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Yokokawa
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T
Horio
T
T
Takeda
D000262:Adenylyl Cyclases / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000494:pharmacology; D004357:Drug Synergism; D019204:GTP-Binding Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000527:Alprostadil; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine