Publication: Endothelin-1 [1-311 acts as a selective ETA-receptor agonist in the rat adrenal cortex
Authors
Rebuffat, P. ; Malendowicz, L.K. ; Neri, G. ; Nussdorfer, G.G.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Endothelin-1 (ET-1) is a 21-amino acid
residue (ET-1[1-211) hypertensive peptide, which
together with its receptor subtypes A and B (ETA and
ETB) is 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[1-211
is generated from bigET-1 by the endothelin-converting
enzyme (ECE-1). However, recent evidence indicates
the existence of an alternative chymase-mediated
biosynthetic pathway leading to the production of an ET-
1[1-311 peptide, which was found to reproduce the ETA
receptor-mediated vascular effects of ET-l[l-211. We
found that ET-1[1-211, but not ET-1[1-311,
concentration-dependently raised steroid secretion from
dispersed rat adrenocortical cells, its effect being
blocked by the ETB-receptor selective antagonist BQ-
788. 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-l[l-311
was found to be significantly more potent than ET-1[1-
211. Autoradiography showed that in the rat adrenal ET-
1[1-211 displaced the binding of selective ligands to both ETA ( [ 1 2 5 ~ ] ~ ~1-21425) and ETB receptors ( [ 1 2 5 ~ ] ~ ~ -
3020), while ET-l[l-311 eliminates only the binding to
ETA receptors. Collectively, our findings provide strong
evidence that ET-1[1-311 acts in the rat adrenal glands as
a selective ETA-receptor agonist, mainly involved in the
stimulation of ZG proliferative activity.
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