Publication: Endothelin-l enhances thymocyte proliferation in monolaterally adrenalectomized rats with contralateral adrenocortical regeneration
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Date
1998
Authors
Malendowicz, L.K. ; Macchi, Verónica ; Brelinska, R. ; Trejer, M. ; Gottardo, Giuseppe ; 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
Endothelins (ETs) are a family of vasoactive
peptides widely distributed in the body systems, where
they exert pleiotropic biological effects, acting through
two main subtypes of receptors, named ETA and ETB.
Evidence indicates that ET-1 plays a permissive role in
the development of neural crest-derived structures,
among which are the epithelia1 cells of the thymus.
These cells are known to control proliferation and
differentiation of thymocytes, a process requiring
adequate levels of glucocorticoids. Therefore, we have
investigated the effects of ET-1, that binds both ETA and
ETB receptors, on thymocyte proliferation in monolaterally
adrenalectomized rats with contralateral
enucleated adrenal at day 4 and 8 of regeneration, when
glucocorticoid production is very low and, respectively,
rather normal. Metaphase index (percentage of
metaphase arrested cells) of thymocytes is the lowest at
day 4 of regeneration, and markedly rose at day 8,
thereby confirming the need of sizable levels of
circulating glucocorticoid for the maintenance of a
normal rate of thymocyte proliferation. ET-l markedly
increased the mitotic index of thymocytes at both times
of adrenal regeneration. At day 8 of regeneration, the
ETA-receptor antagonist BQ-123 markedly lowered
mitotic index of thymocytes, and annulled its ET-1-
evoked raise. Conversely, the ETB-receptor antagonist
BQ-788 was ineffective. Collectively, these findings clearly indicate that endogenous ETs, through the
activation of ETA receptors, are involved in the
maintenance and stimulation of thymocyte proliferation
in the adult rat, thereby playing a possibly important role
in the modulation of the immune-system functions.
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