The present study identified physiological factors which influence the generation (and degradation) of cyclic AMP (cAMP) in the arterial chemoreceptor tissue of the mammalian carotid body. Experiments established a 3-way correlation between cAMP generation, neurotransmitter release from chemoreceptor cells, and carotid sinus nerve (CSN) activity. Incubation of carotid bodies in vitro for 10 min in media equilibrated with different low O2 ('hypoxic') gas mixtures (5% O2 or 10% O2, balance N2) elevated basal cAMP levels (100% O2 media) in proportion to the stimulus intensity. Similar experiments using nodose sensory ganglia showed that low O2 stimulation did not alter cAMP levels in this non-chemosensory tissue. However, the adenylate cyclase (AC) activator, forskolin (10 microM), evoked large increases in the cyclic nucleotide content in both carotid bodies and nodose ganglia. After chronic (10 days) CSN denervation or sympathectomy, the basal levels of cAMP in the carotid body were elevated; the cAMP response to low O2 media (stimulus minus control) was increased after CSN denervation but remained unaltered after sympathectomy. The effects of zero Ca2+ media on cAMP generation was examined in order to assess whether feedback from released neurotransmitters acting on known (presynaptic) type I cell receptors could have contributed to the observed changes in cAMP. Basal levels of cAMP were increased 2.8-fold, and the response to hypoxic stimulation was elevated 5-fold, in the absence of extracellular Ca2+. Forskolin (10 microM) did not alter basal release of [3H]-catecholamines ([3H]CA; synthesized from [3H]tyrosine), or resting CSN discharge; however, stimulus-evoked [3H]CA release and CSN discharge were potentiated in the presence of forskolin.(ABSTRACT TRUNCATED AT 250 WORDS)