Multiple signaling pathways involved in the effect of endothelin type B receptor in rat median eminence.
We assessed the possible link between endothelin receptor mediated phosphoinositide breakdown and NO/cGMP signaling pathways in rat arcuate nucleus-median eminence fragments (AN-ME), brain structures known to contain a rich plexus of nitric oxide synthase (NOS)-containing neurons and fibers, together with densely arranged endothelin ETB-receptors-like immunoreactive fibres. Our data show that ET-1, ET-3 and the ETB-receptors agonist, IRL 1620, increased inositol monophosphate (InsP1) accumulation, NOS activity and cGMP formation, in a similar degree. The stimulatory effect of ETs on InsP1 accumulation and cGMP formation was inhibited by the phospholipase C (PLC) inhibitor, neomycin, and the absence of extracellular calcium, suggesting that calcium is involved in endothelin receptor-induced PLC activation. The L-arginine analog, L-NAME, inhibited ET-1 or IRL1620-stimulated cGMP formation. The ETA receptor antagonists BQ 123, did not alter, while the ETB receptor antagonists BQ788 inhibited ETs-induced increase in the PI metabolism, NOS activity and cGMP generation. Our data indicate that in AN-ME, ETB receptor signals through receptor-mediated calcium dependent-stimulation of phosphoinositide breakdown and activation of NOS/cGMP signaling pathway.
Mathison
Yaira
Y
School of Medicine José María Vargas, Universidad Central de Venezuela, Caracas, Venezuela.
del Garrido
María Rosario
MR
Israel
Anita
A
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D019334:Endothelin-3 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008473:Median Eminence / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D016232:Endothelins; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010446:Peptide Fragments; D010716:Phosphatidylinositols; D010880:Piperidines; D011500:Protein Synthesis Inhibitors; D044023:Receptor, Endothelin B; C074308:sovateltide; D009569:Nitric Oxide; C086539:BQ 788; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D009355:Neomycin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester