Role of endothelin type B receptor in NO/cGMP signaling pathway in rat median eminence.
We studied the effect of endothelins (ETs) on receptor-mediated NO/cGMP signaling in rat arcuate nucleus-median eminence (AN-ME) fragments, an hypothalamic structure known to contain a rich plexus of nitric oxide synthase (NOS)-containing neurons and fibers together with densely arranged ET(B)-receptor-like immunoreactive fibers. NOS activity was determined measuring the conversion of [3H] arginine to [3H] citrulline, as an index of NO produced. cGMP production was determined by radio immunoassay. ET-1, ET-3, and the selective ET(B) receptor agonist, IRL1620, significantly increased cGMP formation and NOS activity. Preincubation of AN-ME fragment with L-arginine analog, N-nitro-L-arginine (L-NAME), inhibited ET-1 or IRL1620-stimulated cGMP formation. The addition of theselective ET(B) receptor antagonist, BQ788, blocked ET-1-, ET-3-, or IRL1620-induced increase in NOS activity and cGMP generation, while BQ123, a selective ET(A) receptor antagonist, was ineffective. Our results demonstrate that in whole rat AN-ME fragments, ETs stimulate NO/cGMP signaling pathway through the interaction with the ET(B) receptor subtype, supporting the concept that ETs may represent an important regulator of reproductive and neuroendocrine function.
Mathison
Yaira
Y
School of Medicine José María Vargas, Universidad Central de Venezuela, Caracas, Venezuela.
Israel
Anita
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008473:Median Eminence / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology; D026602:Nitrergic Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D009569:Nitric Oxide; C086539:BQ 788; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester