Effects of pentobarbital on purinergic P2X receptors of rat dorsal root ganglion neurons.
Purinergic P2X receptors are ligand-gated ion channels that are activated by extracellular adenosine triphosphate (ATP) and are widely expressed not only in the central and peripheral nervous system but also in tissues throughout the body, playing an important role in the transfer of nociceptive information. Since the influence of barbiturates on P2X receptor subtypes is not known, we studied the effects of pentobarbital sodium (PB) on ATP responses in dorsal root ganglion (DRG) neurons. DRG neurons were dissected from 10- to 14-day-old rats and dissociated after enzyme treatment. Electrical measurements were performed using the nystatin-perforated patch recording mode under voltage-clamp conditions. Drugs were applied using the Y-tube method. ATP evoked three types of inward current at -60 mV: fast desensitizing, slow desensitizing, and mixed. The fast-type current was attributed to activation of P2X3 subtype and the slow type to the P2X2 subtype. PB suppressed the fast-type current in a concentration-dependent manner, while the slow type was slightly reduced. A noncompetitive inhibition was suggested by a downward shift of the ATP concentration-response curves. The current-voltage relationships showed inward rectification, and the extent of suppression was not affected by the holding potential. The reduction was greater in external solutions of higher pH. PB had subtype-specific effects on P2X receptors. The ionized form is likely to be responsible for the suppression of the P2X3 receptor current, which may result in a reduction of the excitability of central and peripheral neurons and may contribute to the anesthetic and analgesic actions of the agent.
Kitahara
Seiko
S
Department of Dental Anesthesiology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan. seiko@dent.kyushu-u.ac.jp
Yamashita
Megumi
M
Ikemoto
Yoshimi
Y
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004553:Electric Conductivity; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058477:Receptors, Purinergic P2X3; D009435:Synaptic Transmission / Q000187:drug effects
D006993:Hypnotics and Sedatives; C546410:P2rx3 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate; D010424:Pentobarbital