Liske S, Morris M E
Department of Pharmacology, University of Toronto, ON, Canada.
Can J Physiol Pharmacol. 1994 Apr;72(4):368-74. doi: 10.1139/y94-054.
Effects of the inhibitory neurotransmitter, GABA (gamma-aminobutyric acid) on the excitability of myelinated fibers of isolated amphibian sciatic nerves and their dorsal and ventral spinal roots have been compared with those of a GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), and the GABAB agonist baclofen. Graded, prolonged increases in the amplitude of A-fiber half-maximal compound action potentials of Rana ballenderi sciatic nerves were evoked by GABA (Rmax = 49%, EC50 = 0.1 mM); responses to THIP were smaller (Rmax = 34%, EC50 = 1.1 mM) and with a different, distinctly biphasic recovery phase. In studies of Rana catesbeiana nerves and their attached spinal roots, excitability increases produced in fibers of the ventral roots by GABA were smaller than those of the dorsal roots. Peak changes evoked by THIP in both roots were similar to the effects of GABA on the ventral root; however, THIP's ventral root response showed much less sensitivity and was followed by a rapid recovery phase, undershoot, and secondary, prolonged enhancement. Bicuculline methiodide antagonized agonist-induced increases, and revealed the presence of significant decreases in excitability of the ventral root fibers at concentrations of GABA or THIP < 3 mM. Baclofen evoked inconsistent changes in the excitability of whole nerve and root fibers; small increases occurred with lower doses and secondary, delayed decreases with higher doses. The high concentration (> or = 0.1 mM) of the active isomer needed to cause a small response suggests a limited contribution and (or) presence of GABAB receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
已将抑制性神经递质γ-氨基丁酸（GABA）对离体两栖类坐骨神经及其背根和腹根有髓纤维兴奋性的影响，与GABAA激动剂4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇（THIP）和GABAB激动剂巴氯芬的影响进行了比较。在牛蛙坐骨神经的A纤维半最大复合动作电位幅度上，GABA可引起分级、持续的增加（最大反应率Rmax = 49%，半数有效浓度EC50 = 0.1 mM）；对THIP的反应较小（Rmax = 34%，EC50 = 1.1 mM），且恢复阶段不同，明显呈双相。在研究牛蛙神经及其相连的脊髓根时，GABA对腹根纤维兴奋性的增加小于背根。THIP在两根中引起的峰值变化与GABA对腹根的作用相似；然而，THIP对腹根的反应敏感性低得多，随后是快速恢复阶段、超射和继发性、持续增强。甲磺酸荷包牡丹碱拮抗激动剂诱导的增加，并揭示在GABA或THIP浓度< 3 mM时，腹根纤维兴奋性有显著降低。巴氯芬对全神经和根纤维兴奋性的影响不一致；低剂量时出现小的增加，高剂量时出现继发性、延迟的降低。引起小反应所需的活性异构体高浓度（≥ 0.1 mM）表明GABAB受体的贡献有限和（或）存在。（摘要截断于250字）
