Inhibition by L-arginine of the endothelin-mediated increase in cytosolic calcium in human neutrophils

Abstract The effect of endothelin (ET) on the cytosolic-free calcium ([Ca 2+ ] i ) changes in polymorphonuclear leukocytes (PMN) from normal humans and Wistar rats was investigated. ET induced a dose-related [Ca 2+ ] i peak. This [Ca 2+ ] i transient was blunted by TMB-8 (10 −5 M) and by Ca 2+ -free EGTA medium, therefore suggesting a role of both intracellular Ca 2+ release and Ca 2+ influx in the generation of the [Ca 2+ ] i peak. Preincubation of PMN with the nitric oxide (NO)-donor L-arginine (L-Arg) markedly blocked the ET-induced [Ca 2+ ] i transient in an enantiomerically-specific manner. A similar blunting effect of L-Arg on the fMLP (10 −7 M)-induced [Ca 2+ ] i transient was detected. The L-Arg antagonist, N G -monomethyl-L-arginine (L-NMMA), reverted the L-Arg blocking effect on both ET- and fMLP-induced [Ca 2+ ] i transients. These data suggest that ET has a potential role in activating Ca 2+ mobilization in PMN, an effect that can be inhibited by L-Arg.