Propofol, a general anesthetic administered intravenously, may cause pain at the injection site. The pain is in part due to irritation of vascular endothelial cells. We here investigated the effects of propofol on Ca2+transport and pain mediator release in human umbilical vein endothelial cells (EA.hy926). Propofol mobilized Ca2+from cyclopiazonic acid (CPA)-dischargeable pool but did not cause Ca2+release from the lysosomal Ca2+stores. Propofol-elicited Ca2+release was suppressed by 100 M ryanodine, suggesting the participation of ryanodine receptor channels. Propofol did not affect ATP-triggered Ca2+release but abolished the Ca2+influx triggered by ATP; in addition, propofol also suppressed store-operated Ca2+entry elicited by CPA. Ca2+clearance during CPA-induced Ca2+discharge was unaffected by a low Na+(50 mM) extracellular solution, but strongly suppressed by 5 mM La3+(an inhibitor of plasmalemmal Ca2+pump), suggesting Ca2+extrusion was predominantly through the plasmalemmal Ca2+pump. Propofol mimicked the effect of La3+in suppressing Ca2+clearance. Propofol also stimulated release of pain mediators, namely, reactive oxygen species and bradykinin. Our data suggest propofol elicited Ca2+release and repressed Ca2+clearance, causing a sustained cytosolic [Ca2+]i elevation. The latter may cause reactive oxygen species and bradykinin release, resulting in pain.
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