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

Neurosci Lett. 2003 Mar 6;338(3):181-4. doi: 10.1016/s0304-3940(02)01369-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Baclofen / pharmacology
  • Benzylamines / pharmacology
  • Cells, Cultured
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Antagonists
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Neurons / metabolism*
  • Organophosphorus Compounds / pharmacology
  • Patch-Clamp Techniques
  • Phosphinic Acids / pharmacology
  • Picrotoxin
  • Rats
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • Receptors, GABA-B / drug effects
  • Receptors, GABA-B / metabolism*
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2X3
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Benzylamines
  • GABA Agonists
  • GABA Antagonists
  • GABA-A Receptor Antagonists
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • Organophosphorus Compounds
  • P2rx3 protein, rat
  • Phosphinic Acids
  • Receptors, GABA-A
  • Receptors, GABA-B
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X3
  • Picrotoxin
  • 3-aminopropyl(methyl)phosphinic acid
  • CGP 52432
  • gamma-Aminobutyric Acid
  • Adenosine Triphosphate
  • Baclofen