Phorbol esters and diacylglycerol inhibit vasopressin-induced increases in cytoplasmic-free Ca2+ and 45Ca2+ efflux in Swiss 3T3 cells.
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.
Mendoza
S A
SA
Lopez-Rivas
A
A
Sinnett-Smith
J W
JW
Rozengurt
E
E
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation; D005246:Feedback; D005347:Fibroblasts / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism
D004075:Diglycerides; D005989:Glycerides; D010703:Phorbol Esters; D001127:Arginine Vasopressin; D015240:Phorbol 12,13-Dibutyrate; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D002118:Calcium