Nitric oxide-generating system as an autocrine mechanism in human polymorphonuclear leucocytes.
Recent data [Lopéz-Farré, Riesco, Moliz, Egido, Casado, Hernando and Caramelo (1991) Biochem. Biophys. Res. Commun. 178, 884-891] revealed that endothelin 1 (ET-1) increases intracellular free [Ca2+] in polymorphonuclear leucocytes (PMN) by a mechanism that can be inhibited by L-arginine. The aim of the present study was to clarify the mechanisms of the interaction between the effects of ET-1 and L-arginine in human PMN. The experimental findings showed that in human PMN: (a) ET-1 and the chemoattractant peptide N-formylmethionyl- leucyl-phenylalanine (fMLP) induce both the metabolism of L-arginine to L-citrulline and cyclic GMP (cGMP) formation; (b) the ET-1-induced cGMP production is inhibitable by the L-arginine antagonist NG-monomethyl-L-arginine, therefore suggesting the involvement of NO; (c) the ET-1- or fMLP-induced NO/cGMP stimulation is critically dependent on the availability of L-arginine; (d) human PMN possess a L-arginine transport system with both Na(+)-dependent and -independent components; (e) the L-arginine transport system in PMN appears to be feedback-regulated by NO/cGMP in ET-1-stimulated conditions, but not under baseline conditions; (f) the L-arginine transport system in PMN is independent of the gamma-glutamyl cycle and is not modified by either ET-1 or fMLP. The L-arginine/NO/cGMP-dependent mechanisms characterized in the present study may be relevant in the regulation of PMN activation in pathophysiological conditions in vivo.
Riesco
A
A
Laboratorio de Nefrología, Fundación Jiménez Díaz, Madrid, Spain.
Caramelo
C
C
Blum
G
G
Montón
M
M
Gallego
M J
MJ
Casado
S
S
López Farré
A
A
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002956:Citrulline / Q000097:blood; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood*; D009599:Nitroprusside / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D016232:Endothelins; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D002956:Citrulline; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D001120:Arginine; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine