Elevation of cytosolic free calcium by platelet-activating factor in cultured rat mesangial cells.
Rat glomerular mesangial cell monolayers loaded with the fluorescent probe fura-2 responded to exogenous platelet-activating factor (PAF) with a rapid increase in cytosolic free calcium concentration ([Ca2+]i). PAF-induced [CA2+]i transients consisted of a dose-dependent phasic peak response followed by a sustained tonic phase of increased [Ca2+]i. Chelation of extracellular calcium with EGTA suppressed the tonic phase of increased [Ca2+]i but did not affect the phasic peak response. This suggests two mechanisms for the elevation of [Ca2+]i: a transient mobilization from intracellular stores and an enhanced calcium influx across the plasma membrane, possibly mediated by receptor-operated channels. Lyso-PAF had no effect on basal [Ca2+]i and the PAF-receptor antagonist L652,731 selectively inhibited responses to PAF. PAF-stimulated mesangial cells displayed homologous desensitization to reexposure to PAF while still being responsive to other calcium-mobilizing agonists. Preincubation of cells with the protein kinase C (PKC) activator phorbol myristate acetate diminished the PAF-induced [Ca2+]i transient, suggesting a regulatory role for PKC in PAF-activation of mesangial cells. An increase in [Ca2+]i, as a result of receptor-linked activation of phospholipase C, may mediate PAF-induced hemodynamic and inflammatory events in renal glomeruli.
D000818:Animals; D001572:Benzofurans / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D016257:Fura-2; D005920:Glomerular Mesangium / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism
D001572:Benzofurans; D007473:Ion Channels; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2