Resumen

GARRIDO, M del R  y  ISRAEL, A. Los Fosfoinositidos como señalización de las Endotelinas en la eminencia media y el órgano subfornical de la Rata. AVFT [online]. 2002, vol.21, n.1, pp.91-98. ISSN 0798-0264.

 Endothelin-1 is an endothelium derived peptide with potent vasoconstrictor effects. There are three endothelin (ETs) isoforms: ET-1, ET-2 and ET-3 which have the capacity to bind to two receptor subtypes designated as ET_A and ET_B. It has been demonstrated that central administration of endothelin isoforms induces autonomic and cerebrovascular actions, which suggest a key role for these peptides in the SNC. Endothelins are able to activate different second messengers systems. It has been shown that the ETs receptors in the SNC are coupled to the activation of the phospholipase C and the subsequent increase of inositol trisphosphate (IP₃) levels. Consistent with the presence of a high density receptors in the subfornical organ (SFO) and the median eminence (ME) of the rat brain, our results show an increase in phosphoinositides (PI) hydrolysis induced by endothelins in the SFO and ME, in a dose-dependent manner and with similar ED₅₀ values, suggesting that this effect is mediated by the ET_B receptor. The receptor mediating this effect was further characterized, with the use of selective agonists and antagonists of both receptor subtypes. BQ 123 and BQ 610, two selective antagonists of ET_A receptor, did not altered the ETs-induced increase in the PI turnover. Meanwhile, IRL 1620, a selective agonist of the ET_B receptor subtype, increased the InsP₁ accumulation in the SFO and the ME in a similar degree as endothelins, and this effect was completely blocked by BQ 788, a selective antagonist of this receptor subtype. Our results demonstrate that in the SFO and the ME of the rat brain, ET-1- and ET-3-induced phosphoinositides turnover in mediated through the ET_B receptor.

Palabras clave : Endothelin; Subfornical organ; Median eminence; Receptors; Signaling.