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) A2breceptors 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 EC50was shifted to the right from ∼21 μM Ado in Nox cells to ∼78 μM in CHox cells. Ado-evoked secretion in Nox and CHox cells was markedly inhibited by MRS-1754, an A2breceptor blocker, but was unaffected by SCH-58261, an A2areceptor blocker. Similarly, MRS-1754, but not SCH-58261, partially inhibited high-K+-evoked catecholamine secretion, suggesting a contribution from paracrine activation of A2breceptors by endogenous Ado. CB chemostimuli, acid hypercapnia, and hypoxia elicited a MRS-1754-sensitive rise in intracellular Ca2+that was more robust in CHox and DFX than Nox cells. Taken together, these data suggest that paracrine Ado A2breceptor signaling contributes to stimulus-evoked catecholamine secretion in Nox and CHox CB chemoreceptors; however, the effects of Ado are more robust after CHox.
Muscarinic and nicotinic receptors raise intracellular Ca2+ levels in rat carotid body type I cells.
