The ATP-mediated fast current of rat DRG neurons is a novel effector for GABAB receptor activation

Because γ-aminobutyric acidB (GABAB) agonists produce strong antinociception, the present study analyzed if GABAB receptors might operate through depression of P2X3 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 GABAB 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 GABAB antagonist CGP-52432 blocked the action of SKF-97541, suggesting a GABAB receptor-mediated mechanism (the GABAA antagonist picrotoxin was ineffective). It is suggested that, on nociceptive DRG neurons, GABA produced slow inhibition of P2X3 receptors via metabotropic GABAB receptors. © 2002 Elsevier Science Ireland Ltd. All rights reserved.