Inhibitory and stimulatory effects of phorbol ester on vasopressin-induced cellular responses in cultured rat aortic smooth muscle cells

• Published in: The Journal of biological chemistry Vol. 265; no. 18; pp. 10451 - 10457
• Main Authors: CHARDONNENS, D, LANG, U, ROSSIER, M. F, CAPPONI, A. M, VALLOTTON, M. B
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25-06-1990
• Subjects: Alkaloids - pharmacology; Animals; Aorta - drug effects; Aorta - metabolism; Arginine Vasopressin - antagonists & inhibitors; Arginine Vasopressin - pharmacology; Biological and medical sciences; Calcimycin - pharmacology; Calcium - metabolism; Cell physiology; Cells, Cultured; Cytosol - enzymology; Drug Synergism; Enzyme Activation; Epoprostenol - biosynthesis; Female; Fundamental and applied biological sciences. Psychology; Inositol 1,4,5-Trisphosphate - metabolism; Kinetics; Molecular and cellular biology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; phorbol 12-myristate 13-acetate diester; prostacyclin; Protein Kinase C - metabolism; Rats; Rats, Inbred Strains; Signal transduction; smooth muscle; Staurosporine; Tetradecanoylphorbol Acetate - pharmacology; vasopressin; Signal transduction; Vertebrata; Protein kinase C; Mammalia; Calcium; Prostaglandin I2; Rat; Rodentia; Aorta; Smooth muscle; Inositol phosphate; Vasopressin
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)86968-X

In rat aortic smooth muscle cells, vasopressin (AVP) induces prostacyclin (PGI2) production, probably as the consequence of
phospholipase C activation. Our study analyzes the effects of phorbol 12-myristate 13-acetate (PMA)-induced protein kinase
C (PKC) activation on AVP-induced inositol 1,4,5-trisphosphate formation, cytosolic free Ca2+ concentration [( Ca2+]c), and
PGI2 production. PMA rapidly decreased PKC activity in the cytosol of smooth muscle cells, while increasing it transiently
in the membranes with a maximum around 20 min. Prior exposure of the cells to PMA resulted in a transient inhibition of both
AVP-induced inositol 1,4,5-trisphosphate formation and [Ca2+]c rise. This was inversely correlated with membraneous PKC activity
and partially reversed by the PKC inhibitor staurosporine. In contrast, pretreating the cells with PMA markedly potentiated
A23187 or AVP-induced PGI2 production. Under those conditions, AVP-induced PGI2 production did not correlate either with PMA-induced
membranous PKC activity or with AVP-induced PLC activation. However, this potentiating effect of PMA was reversed by staurosporine
and was not mimicked by the 4 alpha-phorbol, an inactive analogue of PMA. Thus, the possibility is raised that, while inhibiting
AVP-induced PLC activation, PMA-induced PKC activation increases the Ca2+ sensitivity of the cellular signaling system leading
to PGI2 production.