Inhibitory and stimulatory effects of phorbol ester on vasopressin-induced cellular responses in cultured rat aortic smooth muscle cells
| Autor: | D. Chardonnens, Michel B. Vallotton, Alessandro M. Capponi, Michel F. Rossier, U. Lang |
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| Rok vydání: | 1990 |
| Předmět: |
chemistry.chemical_classification
Vasopressin medicine.medical_specialty Prostacyclin Cell Biology Biology Biochemistry Cell biology Cytosol chemistry.chemical_compound Endocrinology chemistry Internal medicine medicine Phorbol Staurosporine Inositol Inositol phosphate Molecular Biology hormones hormone substitutes and hormone antagonists Protein kinase C medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 265:10451-10457 |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/s0021-9258(18)86968-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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