The ATP-mediated fast current of rat dorsal root ganglion neurons is a novel effector for GABA(B) receptor activation.

Because gamma-aminobutyric acid(B) (GABA(B)) agonists produce strong antinociception, the present study analyzed if GABA(B) receptors might operate through depression of P2X(3) receptors responsible for fast adenosine triphosphate (ATP) currents involved in transmitting pain. On rat dorsal root ganglion (DRG) nociceptive neurons, inward currents induced by ATP were inhibited after 2 s or 60 s GABA application and unaffected after 10 s application. SKF-97541 or baclofen, potent GABA(B) agonists, mimicked only the late inhibition of ATP currents. The effect of SKF-97541 or GABA was observed even after their transient application prior to ATP. The GABA(B) antagonist CGP-52432 blocked the action of SKF-97541, suggesting a GABA(B) receptor-mediated mechanism (the GABA(A) antagonist picrotoxin was ineffective). It is suggested that, on nociceptive DRG neurons, GABA produced slow inhibition of P2X(3) receptors via metabotropic GABA(B) receptors.