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.

6 Figures and Tables


Citations per Year

358 Citations

Semantic Scholar estimates that this publication has 358 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Riesco1993NitricOS, title={Nitric oxide-generating system as an autocrine mechanism in human polymorphonuclear leucocytes.}, author={Andres Riesco and Carlos A. Caramelo and Greg Blum and Mercedes Mont{\'o}n and Miren J. Gallego and Santos Casado and A J L{\'o}pez Farr{\'e}}, journal={The Biochemical journal}, year={1993}, volume={292 ( Pt 3)}, pages={791-6} }