Phorbol ester and atrial natriuretic peptide receptor response on vascular smooth muscle.
At least two types of receptors for natriuretic peptides have been reported: biologically active receptors coupled with guanylate cyclase (atrial natriuretic peptide [ANP]-B receptors) and clearance receptors (ANP-C receptors). To elucidate the role of protein kinase C (PKC) in the regulation of ANP-B receptors, vascular smooth muscle cells in culture were treated with phorbol ester. Incubation with receptor agonists and phorbol ester led to the desensitization of receptor-mediated cyclic guanosine monophosphate (ANP-B receptor response) in rat vascular smooth muscle cells. Although a PKC inhibitor and downregulation of PKC by long-term incubation of cells with phorbol esters blocked the phorbol ester-induced desensitization of the ANP-B receptor response, they did not block the ANP-induced desensitization of the ANP-B receptor response. In addition, when desensitization by phorbol esters was observed, ANP was still capable of desensitization. These observations suggest that the mechanism for regulating ANP-B receptor sensitivity may be both PKC-dependent and PKC-independent and mediated by phorbol esters and ANP, respectively.
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
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006162:Guanylate Cyclase / Q000096:biosynthesis*; D007546:Isoquinolines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007546:Isoquinolines; D009419:Nerve Tissue Proteins; D010879:Piperazines; D011956:Receptors, Cell Surface; D020097:Natriuretic Peptide, Brain; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate