Mechanism of cellular effect of phorbol esters on action of arginine vasopressin and angiotensin II on rat vascular smooth muscle cells in culture.
The inhibitory effect of phorbol-12-myristate-13-acetate (PMA) on the Ca2+-mobilization mechanisms by arginine vasopressin (AVP) and angiotensin II (AII) was analysed in rat vascular smooth muscle cells (VSMC) in culture. PMA inhibited the Ca2+-mobilizing effect of both AVP and AII in a dose-dependent manner, including the rise in cytosolic free Ca2+ ( [Ca2+]i) and Ca2+ efflux. In addition, inositol trisphosphate (IP3) production induced by AVP or AII was more than 50% reduced by PMA. The involvement of protein kinase C was implicated by the diminution of the PMA effect by the specific protein kinase C inhibitor isoquinoline-sulphonyl-O-2-methylpiperazine (H7) and the lack of effect of an inactive phorbol. Thus, these results suggest that there is a blocking site that is common or similar for both AVP and AII signal transduction, and that it is a substrate for protein kinase C. This blocking action of protein kinase C occurred at least in part by inhibition of IP3 production and, subsequently, a reduction in cytosolic Ca2+ release. In the presence of ionomycin, which produces an increase in [Ca2+]i that is not altered by PMA, 45Ca2+ efflux was increased instead of inhibited by PMA, thus suggesting that protein kinase C activation also stimulates a Ca2+-extrusion mechanism in VSMC.
Caramelo
C
C
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Tsai
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P
Schrier
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RW
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003864:Depression, Chemical; D004987:Ethers / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D015759:Ionomycin; D007546:Isoquinolines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004987:Ethers; D007295:Inositol Phosphates; D007546:Isoquinolines; D010879:Piperazines; D000804:Angiotensin II; D001127:Arginine Vasopressin; D015759:Ionomycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium