Kitahara Seiko, Yamashita Megumi, Ikemoto Yoshimi
Department of Dental Anesthesiology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Can J Physiol Pharmacol. 2003 Dec;81(12):1085-91. doi: 10.1139/y03-111.
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.
嘌呤能P2X受体是一种配体门控离子通道，可被细胞外三磷酸腺苷（ATP）激活，不仅在中枢和外周神经系统广泛表达，还在全身各组织中广泛表达，在伤害性信息传递中起重要作用。由于巴比妥类药物对P2X受体亚型的影响尚不清楚，我们研究了戊巴比妥钠（PB）对背根神经节（DRG）神经元ATP反应的影响。从10至14日龄大鼠中分离出DRG神经元，并在酶处理后进行解离。在电压钳制条件下，使用制霉菌素穿孔膜片钳记录模式进行电生理测量。采用Y型管法施加药物。在-60 mV时，ATP诱发三种内向电流：快速脱敏电流、缓慢脱敏电流和混合电流。快速型电流归因于P2X3亚型的激活，缓慢型电流归因于P2X2亚型的激活。PB以浓度依赖的方式抑制快速型电流，而缓慢型电流略有降低。ATP浓度-反应曲线向下移位提示存在非竞争性抑制。电流-电压关系呈内向整流，抑制程度不受钳制电位的影响。在较高pH值的外部溶液中，抑制作用更强。PB对P2X受体具有亚型特异性作用。离子化形式可能是抑制P2X3受体电流的原因，这可能导致中枢和外周神经元兴奋性降低，并可能有助于该药物的麻醉和镇痛作用。
