PHARMACOLOGICAL PROPERTIES OF P2X(3)-RECEPTORS PRESENT IN NEURONS OF THE RAT DORSAL-ROOT GANGLIA

1 The electrophysiological actions of several agonists which may diffe rentiate between P2X(1)- and P2X(3)-receptors were studied under conce ntration and voltage-clamp conditions in dissociated neurones of 1-4 d ay old rat dorsal root ganglia. 2 beta,gamma-Methylene-D-ATP (beta,gam ma-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 (A P4A) (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,gam ma-me-D-ATP and AP5A and ATP had similar maximum values, while that fo r AP4A had a lower maximum. The concentration-response curve to UTP wa s shallow and did not reach a maximum. beta,gamma-Methylene-L-ATP was virtually inactive. The rank order of agonist potency was ATP > AP5A a pproximate to AP4A > beta,gamma-me-D-ATP > UTP > > beta,gamma-methylen e-L-ATP. 4 The inward currents were inhibited by the P2-receptor antag onists suramin (100 mu M) and pyridoxalphosphate-6-azophenyl-2',4'-dis ulphonic acid (PPADS) (10 mu M). PPADS also inhibited responses to ATP (800 nM) and alpha,beta-methylene ATP (2 mu M) in a concentration-dep endent 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 evo ke rapid, transient inward currents in dissociated neurones of rat dor sal root ganglia. The very low activity of beta,gamma-methylene-L-ATP suggests that the agonists were acting at the P2X(3)-subtype to produc e these effects.