Abstract
To identify the mechanisms of P2X(3) receptor inhibition by extracellular cyclic adenosine monophosphate (cAMP) in rat dorsal root ganglion (DRG) neurones. Whole-cell currents were measured in cultured DRG neurones using the combination of voltage and concentration clamp. We have found that extracellular cAMP inhibits P2X(3)-mediated currents in a concentration- and use-dependent manner. The P2X(3) currents, activated by ATP applied every 4 min, were inhibited by 55% in the presence of 10 microm cAMP and by 81% in the presence of 30 microm 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 mum adenosine. 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.
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