Extracellular cAMP inhibits P2X₃ receptors in rat sensory neurones through G protein-mediated mechanism

Aim: To identify the mechanisms of P2X₃ receptor inhibition by extracellular cyclic adenosine monophosphate (cAMP) in rat dorsal root ganglion (DRG) neurones. Methods: Whole-cell currents were measured in cultured DRG neurones using the combination of voltage and concentration clamp. Results: We have found that extracellular cAMP inhibits P2X₃-mediated currents in a concentration- and use-dependent manner. The P2X₃ currents, activated by ATP applied every 4 min, were inhibited by 55% in the presence of 10 μm cAMP and by 81% in the presence of 30 μm cAMP. At 8 min interval between ATP applications the same concentration of cAMP did not alter the currents. Addition of 0.5 mm of guanosine 5′-O-(2-thiodiphosphate) to intracellular solution blocked the inhibitory action of cAMP. The inhibitory effects of cAMP were not mimicked by extracellular application of 30 μm adenosine. Conclusions: In this paper, we demonstrate, for the first time, that extracellular application of cAMP to rat sensory neurones inhibits P2X ₃ receptors via a G protein-coupled mechanism in a use-dependent manner, thus indicating the neuronal expression of specific plasmalemmal cAMP receptor.