Pharmacological properties of P2X3-receptors present in neurones of the rat dorsal root ganglia

1 The electrophysiological actions of several agonists which may differentiate between P2X(1)- and P2X(3)-receptors were studied under concentration and voltage-clamp conditions in dissociated neurones of 1-4 day old rat dorsal root ganglia. 2 beta,gamma-Methylene-D-ATP (beta,gamma-me-D-ATP) (1-300 mu M), diadenosine 5',5'''-P-1,P-4-pentaphosphate (AP5A) (100 nM-300 mu M) diadenosine 5',5'''-P-1,P-4-tetraphosphate (AP4A) (300 nM-300 mu M) and uridine 5'-triphosphate (UTP) (1 mu M-1 mM) all activated concentration-dependent inward currents with a latency to onset of a few ms. 3 The concentration-response curves for beta,gamma-me-D-ATP and AP5A and ATP had similar maximum values, while that for AP4A had a lower maximum. The concentration-response curve to UTP was shallow and did not reach a maximum. beta,gamma-Methylene-L-ATP was virtually inactive. The rank order of agonist potency was ATP > AP5A approximate to AP4A > beta,gamma-me-D-ATP > UTP > > beta,gamma-methylene-L-ATP. 4 The inward currents were inhibited by the P2-receptor antagonists suramin (100 mu M) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (10 mu M). PPADS also inhibited responses to ATP (800 nM) and alpha,beta-methylene ATP (2 mu M) in a concentration-dependent manner. 5 This study shows that beta,gamma-me-D-ATP, AP5A, AP4A and UTP all act via a suramin-and PPADS-sensitive P2X-receptor to evoke rapid, transient inward currents in dissociated neurones of rat dorsal root ganglia. The very low activity of beta,gamma-methylene-L-ATP suggests that the agonists were acting at the P2X(3)-subtype to produce these effects.