We have used the in vitro preparation of the intact carotid body (CB) and isolated chemoreceptor cells to elucidate the distribution and function of alpha2-adrenoreceptors. The significance of the study lies in the fact that norepinephrine (NE), being the neurotransmitter of the sympathetic innervation to the CB, is also abundant in chemoreceptor cells. In intact CB whose catecholamine (CA) deposits had been labeled by prior incubation with the CA precursor [3H]tyrosine, the alpha2-antagonist yohimbine (10 microM) potentiated the low-PO2 (33 and 60 mmHg)-induced release of [3H]CA by 100 and 53%, respectively. Yohimbine (10 microM) and SKF-86466 (50 microM; another alpha2-antagonist) reversed the inhibition of the release of [3H]CA produced by the alpha2-receptor agonists clonidine and UK-14304 (10 microM). The increase in adenosine 3',5'-cyclic monophosphate produced by low PO2 was further augmented by yohimbine and nearly halved by UK-14304 and clonidine. In isolated chemoreceptor cells, UK-14304 and NE inhibited voltage-dependent Ca2+ currents by 28 and 32%, respectively. These results indicate that alpha2-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 CB from normal and chronically sympathectomized animals, we demonstrated a specific accumulation of [3H]NE in intraglomic sympathetic endings. Hypoxia (PO2 approximately 33 mmHg) did not elicit release of [3H]NE from the sympathetic endings, but high extracellular K+ (K+(e)) induced a release of [3H]NE that was inhibited by alpha2-agonists and augmented by alpha2-antagonists. These findings demonstrate that alpha2-receptors are also present in the sympathetic endings of the CB, where they modulate the release of NE. 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 NE.