Endothelin ET(B) receptor subtype mediates nitric oxide/cGMP formation in rat adrenal medulla.
We investigated the effect of endothelins (ETs) on receptor-mediated cGMP formation in whole rat adrenal medulla. ET-3 increased cGMP formation in a concentration-dependent manner; in addition, all three isoforms of ETs, at equimolar doses, increased cGMP levels in similar degree. IRL-1620, a selective ET(B) receptor agonist, also increased cGMP formation, mimicking the effects of ETs, but the increase was higher than those produced by ETs. L-arginine analogue, N-nitro-L-arginine (L-NAME), and methylene blue and OQD, two inhibitors of soluble guanylyl cyclase, significantly inhibited the increase in cGMP production induced by ETs or IRL-1620. Likewise, the selective ET(B) receptor antagonist, BQ-788, significantly inhibited ET-1- or ET-3-induced cGMP generation. Our results demonstrate that in whole rat adrenal medulla, endothelins stimulate NO-induced cGMP generation through ET(B) receptors, and they support the concept that endothelins could play a role in the regulation of adrenal medulla function.
Mathison
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School of Medicine J. M. Vargas, Department of Biological Sciences, Universidad Central de Venezuela, Caracas.
Israel
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A
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D019333:Endothelin-2 / Q000494:pharmacology; D019334:Endothelin-3 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C074308:sovateltide; D009569:Nitric Oxide; C086539:BQ 788; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester