Resumo

MATHISON, Y  e  ISRAEL, A. El Sistema Óxido Nítrico/Gmpc como mecanismo de señalización de las Endotelinas en el Sistema Nervioso. AVFT [online]. 2002, vol.21, n.1, pp.74-82. ISSN 0798-0264.

ABSTRACT We investigated the endothelins (ETs) signaling pathway in two structures of the nervous system related to neuroendocrine control, the median eminence (ME) and adrenal medulla (AM) of the rat. The three isoforms of ETs increased cGMP levels in similar degree and in a concentration-dependent maner. IRL-1620, a selective ET_B receptor agonist, also increased the cGMP formation in both structures. ET_B receptor antagonist, BQ-788 significantly inhibited the increase in ET-1 or ET-3-induced cGMP generation. Additionally, ET-1 stimulated nitric oxide synthase activity in the median eminence and adrenal medulla. In the adrenal medulla ETs or IRL-induced cGMP production was inhibited by L-arginine analogue, L-nitro-arginine-methyl-esther (L-NAME) and by two inhibitors of soluble guanylyl cyclase, methylene blue and ODQ. Our results demonstrated that in median eminece and adrenal medulla, endothelins stimulate NO-induced cGMP generation through ET_B receptors, and they support the concept that endothelins could play a physiological role in nervous system through nitric oxide formation and soluble guanylyl cyclase activation.

Palavras-chave : Endothelins; Nitric oxide; cGMP; ET_B Receptor..