Nitric oxide inhibits GABA-evoked current in dorsal root ganglion neuron via PKG-dependent pathway.
gamma-Aminobutyric acid (GABA) is considered a major inhibitory neurotransmitter in the generation of presynaptic inhibition at central terminals of primary afferent fiber (PAF), while it has also been established that nitric oxide (NO) may sensitize the terminals of nocisponsive PAFs and enhance neuropeptide release, possibly via mechanisms involving the activation of a cyclic guanidine monophosphate (cGMP)-dependent PKG. The present work was undertaken to explore the modulatory effect of sodium nitroprusside (SNP), a donor of NO, on GABA-evoked current of isolated adult rat dorsal root ganglion (DRG) neurons and the intracellular mechanism involved, by means of whole-cell patch clamp recording. The results showed that 1 mM SNP reversibly inhibited the inward current evoked by 0.1 mM GABA (-1.05 +/- 0.17nA vs. -0.63 +/- 0.11nA, n = 22, p < 0.01 or 0.1 mM muscimol a specific GABA(A) receptor agonist (-1.70 +/- 0.39 nA vs. -1.01 +/- 0.24 nA, n = 6, p < 0.05), which could be cancelled by simultaneous application of 1 mM methylene blue, an inhibitor of PKG. After preapplication of SNP with increasing concentrations 0.03, 0.1, 0.3, 1, and 3 mM), SNP inhibited both 0.1 mM GABA-evoked current (IC(50) = 0.2423 mM, n = 5) and 0.1 mM muscimol-evoked current (IC(50) = 0.3255 mM, n = 3) in DRG neurons in a dose-dependent manner. Therefore, it was suggested that PKG-dependent pathway may be involved in the NO-induced inhibition of GABA(A) receptor-mediated inward current in rat DRG neurons, which may be involved in the presynaptic disinhibition of nociceptive information induced by NO under certain conditions.
Bie
B H
BH
Institute of Neurobiology, Fu-Dan University, Shanghai, China.
Zhao
Z Q
ZQ
D000818:Animals; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018755:GABA Agonists; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009118:Muscimol; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D017869:Cyclic GMP-Dependent Protein Kinases; D008751:Methylene Blue