RESUMO
Chronic hypoxia (CHox) augments chemoafferent activity in sensory fibers innervating carotid body (CB) chemoreceptor type I cells; however, the underlying mechanisms are poorly understood. We tested the hypothesis that enhanced paracrine signaling via adenosine (Ado) A2b receptors is involved. Dissociated rat CB cultures were exposed for 24 h to normoxia (Nox, 21% O2) or CHox (2% O2) or treated with the hypoxia mimetic deferoxamine mesylate (DFX), and catecholamine secretion from type I cells was monitored by amperometry. Catecholamine secretion was more robust in CHox and DFX type I cells than Nox controls after acute exposure to acid hypercapnia (10% CO2, pH 7.1) and high K(+) (75 mM). Exogenous Ado increased catecholamine secretion in a dose-dependent manner, and the EC50 was shifted to the right from â¼21 µM Ado in Nox cells to â¼78 µM in CHox cells. Ado-evoked secretion in Nox and CHox cells was markedly inhibited by MRS-1754, an A2b receptor blocker, but was unaffected by SCH-58261, an A2a receptor blocker. Similarly, MRS-1754, but not SCH-58261, partially inhibited high-K(+)-evoked catecholamine secretion, suggesting a contribution from paracrine activation of A2b receptors by endogenous Ado. CB chemostimuli, acid hypercapnia, and hypoxia elicited a MRS-1754-sensitive rise in intracellular Ca(2+) that was more robust in CHox and DFX than Nox cells. Taken together, these data suggest that paracrine Ado A2b receptor signaling contributes to stimulus-evoked catecholamine secretion in Nox and CHox CB chemoreceptors; however, the effects of Ado are more robust after CHox.