Endothelin ETB receptor signaling in the median eminence and subfornical organ of the rat brain.
We investigated the effect of endothelins (ETs) on receptor-mediated phosphoinositides (PI) turnover in whole subfornical organ (SFO) and median eminence (ME). Consistent with the presence of a high density of binding sites in the SFO and the ME of the rat brain, our results show an increase in PI hydrolysis induced by ETs in each structure, in a dose-dependent manner and with similar ED50 values. In addition, IRL 1620, a selective ETB receptor agonist, increased the inositol monophosphate (InsP1) accumulation in the SFO and the ME in a similar degree as ETs. With the use of selective agonists and antagonists of both endothelin receptor subtypes, we characterized the receptor subtype involved in ET-induced phosphoinositide metabolism. The addition of two selective ETA receptor antagonists, BQ 123 or BQ 610, did not alter the ETs-induced increase in the PI metabolism. While, IRL 1620- and ET3-induced InsP1 accumulation was completely blocked by BQ 788, a selective ETB receptor antagonist, in both brain structures evaluated. Our results demonstrate that in the SFO and the ME of the rat brain, stimulation of phosphoinositide turnover constitutes one of the signaling pathways of ETs, and this action is mediated through ETB receptor activation. These results support the concept that endothelin could play a role in the regulation of brain functions.
School of Pharmacy, Laboratory of Neuropeptides, Universidad Central de Venezuela, Apartado Postal 50176, Sabana Grande 1050A, Caracas, Venezuela.
María del Rosario
Mdel R
Garrido
Anita
A
Israel
D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D019334:Endothelin-3 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013356:Subfornical Organ / Q000187:drug effects / Q000378:metabolism*
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010716:Phosphatidylinositols; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C087220:BQ 610; C072247:cyclo(Trp-Asp-Pro-Val-Leu)