Inhibition by L-arginine of the endothelin-mediated increase in cytosolic calcium in human neutrophils.
The effect of endothelin (ET) on the cytosolic-free calcium [(Ca2+]i) changes in polymorphonuclear leukocytes (PMN) from normal humans and Wistar rats was investigated. ET induced a dose-related [Ca2+]i peak. This [Ca2+]i transient was blunted by TMB-8 (10(-5)M) and by Ca(2+)-free EGTA medium, therefore suggesting a role of both intracellular Ca2+ release and Ca2+ influx in the generation of the [Ca2+]i peak. Preincubation of PMN with the nitric oxide (NO)-donor L-arginine (L-Arg) markedly blocked the ET-induced [Ca2+]i transient in an enantiomerically-specific manner. A similar blunting effect of L-Arg on the fMLP (10(-7)M)-induced [Ca2+]i transient was detected. The L-Arg antagonist, NG-monomethyl-L-arginine (L-NMMA), reverted the L-Arg blocking effect on both ET- and fMLP-induced [Ca2+]i transients. These data suggest that ET has a potential role in activating Ca2+ mobilization in PMN, an effect that can be inhibited by L-Arg.
Lopez Farre
A
A
Laboratorio de Nefrologia, Fundacion Jimenez Diaz, Madrid, Spain.
Riesco
A
A
Moliz
M
M
Egido
J
J
Casado
S
S
Hernando
L
L
Caramelo
C
C
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D019323:omega-N-Methylarginine
D016232:Endothelins; D005456:Fluorescent Dyes; C049925:fura-2-am; D019323:omega-N-Methylarginine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D001120:Arginine; D002118:Calcium; D016257:Fura-2