Phorbol esters and diacylglycerol inhibit vasopressin-induced increases in cytoplasmic-free Ca and Ca efflux in Swiss 3T3 cells |
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Authors: | Stanley A Mendoza Abelardo Lopez-Rivas James W Sinnett-Smith Enrique Rozengurt |
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Abstract: | Vasopressin increased intracellular free calcium concentration Ca2+]i in quin-2-loaded quiescent Swiss 3T3 cells. This effect of vasopressin was rapidly inhibited by biologically active tumour promoters including phorbol dibutyrate (PBt2) and by the synthetic diacylglycerol 1-oleoyl-2-acetyl-glycerol (OAG). Prolonged pretreatment of Swiss 3T3 cells with PBt2 causes a loss of protein kinase C activity (Rodriguez-Pena & Rozengurt, Biochem biophys res commun 120 (1984) 1053) 28]. This pretreatment abolished the inhibition by PBt2 or OAG of vasopressin-mediated increases in Ca2+]i. Vasopressin also stimulated 45Ca2+ efflux from cells pre-loaded with the isotope. This effect of the hormone was also inhibited by PBt2. Prolonged pretreatment with PBt2 prevented the inhibition of vasopressin-stimulated 45Ca2+ release by PBt2. Thus, protein kinase C stimulation inhibits vasopressin-mediated increases in Ca2+]i and 45Ca2+ efflux apparently by blocking the increased release of Ca2+ from an intracellular store caused by the hormone. These findings suggest that activation of protein kinase C may act as a feedback inhibitor to modulate ligand-mediated increases in Ca2+]i. |
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