Endothelin-1[1-31] acts as a selective ETA-receptor agonist in the rat adrenal cortex

• Rebuffat, P. ^[1] ; Malendowicz, L.K. ^[1] ; Neri, G. ^[1] ; Nussdorfer, G.G. ^[1]
  1. [1] Department of Human Anatomy and Physiology, Section of Anatomy, Padua, Italy
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 16, Nº. 2, 2001, págs. 535-540
• Idioma: inglés
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• Resumen

  • Endothelin-1 (ET-1) is a 21-amino acid residue (ET-1[1-21]) hypertensive peptide, which together with its receptor subtypes A and B (ETA and ETB) i expressed in the rat adrenal cortex, where it stimulates steroid-hormone (aldosterone and corticosterone) secretion through the ETB receptor and the growth (proliferative activity) of the zona glomerulosa (ZG) through the ETA receptor. ET-1[1-21] i generated from bigET-1 by the endothelin-converting enzyme (ECE-1). However, recent evidence indicates the exi tence of an alternative chymase-mediated biosynthetic pathway leading to the production of an ET1[1-31] peptide, which was found to reproduce the ETA receptor-mediated vascular effects of ET-1[1-21]. We found that ET-1[1-21], but not ET-1[1-31], concentration-dependently raised teroid secretion from dispersed rat adrenocortical cells, its effect being blocked by the ETB-receptor selective antagonist BQ788. Both ET-1s concentration-dependently increased the number of "S-phase" cells (as detected by the 5- bromo-2' -deoxyuridine immunocytochemical method) in capsule-ZG strips within a 240 min incubation. The ZG proliferogenic action of both ET-1s was blocked by the ETA-receptor antagonist BQ-123, and ET-1[1-31] was found to be significantly more potent than ET-1[1- 21]. Autoradiography showed that in the rat adrenal ET1[1-21] displaced the binding of selective ligands to both ETA ([125I]PD-151242) and ETB receptors ([125I]BQ3020), while ET-1[1-31] eliminates only the binding to ETA receptors. Collectively, our findings provide strong evidence that ET-1 [1-31] acts in the rat adrenal glands as a selective ETA-receptor agoni t, mainly involved in the stimulation of ZG proliferative activity.