Mechanisms of [alpha]2-adrenoceptor-mediated inhibition in the
rabbit carotid body.
Almaraz, L., M. T. P[acute]erez-Garc[acute]ia, A. Gom[acute]ez
-Ni[tilde]no, and C. Gonz[acute]alez.
Departamento de Bioqu[acute]imica y Biolog[acute]ia Molecular y
Fisiolog[acute]ia, IBGM. Facultad de Medicina, Universidad de
Valladolid. 47005 VALLADOLID. -Spain-
APStracts 3:0286C, 1996.
We have used the in vitro preparation of the intact carotid body (CB),
and isolated chemoreceptor cells, to elucidate the distribution and
function of [alpha]2-adrenoreceptors. The significance of the study
lies in the fact that noradrenaline (NA), being the neurotransmitter
of the sympathetic innervation to the CB, is also abundant in
chemoreceptor cells. In intact CBs, whose catecholamine (CA) deposits
have been labeled by prior incubation with the CA precursor
[3H]tyrosine, the [alpha]2-antagonist yohimbine (10 [mu]M)
potentiated the low PO2 (33 and 60 mmHg)-induced release of [3H]-CA
by 100% and 53%, respectively. Yohimbine (10 [mu]M) and SKF 8644 (50
[mu]M; another [alpha]2-antagonist) reversed the inhibition of the
release of [3H]-CA produced by the [alpha]2-receptor agonists
clonidine and UK 14,304 (10 [mu]M). The increase in cAMP produced by
low PO2 was further augmented by yohimbine, and nearly halved by UK
14,304 and clonidine. In isolated chemoreceptor cells, UK 14,304 and
NA, inhibited voltage-dependent Ca2+ currents by 28% and 32%,
respectively. These results indicate that [alpha]2-receptors are
present in chemoreceptor cells where they reduce the release of [3H]
-CA. Inhibition of adenylate cyclase(s) and Ca2+ channels may be
involved in this effect. Using intact CBs from normal and chronically
sympathectomized animals, we demonstrated a specific accumulation of
[3H]-NA in intraglomic sympathetic endings. Hypoxia (PO2 nearly equal
to 33 mmHg) did not elicit release of [3H]-NA from the sympathetic
endings, but high K+e-induced a release of [3H]-NA which was
inhibited by [alpha]2-agonists and augmented by [alpha]2-antagonists.
These findings demonstrate that [alpha]2-receptors are also present
in the sympathetic endings of the CB where they modulate the release
of NA. As a whole, this work provides a more detailed understanding
of the role of the sympathetic innervation in the control of the CB
chemoreceptor function, including the cellular mechanisms of the
action of NA.
Received 13 April 1996; accepted in final form 30 August 1996.
APS Manuscript Number C259-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996