MECHANISMS OF ALPHA(2)-ADRENOCEPTOR-MEDIATED INHIBITION IN RABBIT CAROTID-BODY

We have used the in vitro preparation of the intact carotid body (CB) and isolated chemoreceptor cells to elucidate the distribution and fun ction of alpha(2)-adrenoreceptors. The significance of the study lies in the fact that norepinephrine (NE), being the neurotransmitter of th e sympathetic innervation to the CB, is also abundant in chemoreceptor cells. In intact CB whose catecholamine (CA) deposits had been labele d by prior incubation with the CA precursor [H-3]tyrosine, the alpha(2 )-antagonist yohimbine (10 mu M) potentiated the low-P-O2 (33 and 60 m mHg)-induced release of [H-3]CA by 100 and 53%, respectively. Yohimbin e (10 mu M) and SKF-86466 (50 mu M; another alpha(2)-antagonist) rever sed the inhibition of the release of [H-3] CA produced by the alpha(2) -receptor agonists clonidine and UK-14304 (10 mu M). The increase in a denosine 3',S'-cyclic monophosphate produced by low P-O2 was further a ugmented by yohimbine and nearly halved by UK-14304 and clonidine. In isolated chemoreceptor cells, UK-14304 and NE inhibited voltage-depend ent 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 [H-3]CA. Inhibition of adenylate cyclase(s) and Ca2+ channels may be involved in this effect. Using intact CB from no rmal and chronically sumpathectomized animals, we demonstrated a speci fic accumulation of [H-3]NE in intraglomic sympathetic endings. Hypoxi a (P-O2 similar to 33 mmHg) did not elicit release of [H-3]NE from the sympathetic endings, but high extracellular K+ (K-e(+)) induced a rel ease of [H-3]NE that was inhibited by alpha(2)-agonists and augmented by alpha(2)-antagonists. These findings demonstrate that alpha(2)-rece ptors are also present in the sympathetic endings of the CB, where the y modulate the release of NE. As a whole, this work provides a more de tailed understanding of the role of the sympathetic innervation in the control of the CB chemoreceptor function, including the cellular mech anisms of the action of NE.