Padjen A L, Mitsoglou G M, Hassessian H
Department of Pharmacology and Therapeutics, McGill University, Montreal, Que., Canada.
Brain Res. 1989 May 29;488(1-2):288-96. doi: 10.1016/0006-8993(89)90720-8.
It has been reported that 6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1, 1-dioxide (AMBD, TAG) is a specific blocker of taurine and beta-alanine responses in the central nervous system. We have re-examined the effect of AMBD on amino acid and synaptically evoked responses recorded from isolated hemisected frog spinal cords by means of the sucrose gap technique. When indirect responses were blocked by adding tetrodotoxin (0.2 microM) or manganese chloride (2 mM) to the normal Ringer solution, AMBD (0.01-0.5 mM) selectively antagonized taurine, beta-alanine, hypotaurine and kojic amine evoked depolarizations of primary afferents at their intramedullary part (dorsal root terminals, DRT) and on dorsal root ganglia (DRG), without significantly affecting responses to glutamate (on DRT), glycine (on DRT) or GABA (on DRT and DRG). Depolarizing responses to taurine and beta-alanine (1 mM) were depressed by up to 50% with 0.1 mM AMBD and often completely antagonized with 0.25 mM AMBD. In normal Ringer solution, AMBD selectively antagonized the dorsal root potential evoked by ventral root stimulation (VR-DRP, threshold at 0.02 mM AMBD, 90% block with 0.25 mM); other synaptic potentials increased in duration and/or amplitude, demonstrating a strong convulsant effect of AMBD. Thus, the depolarizing responses of taurine, beta-alanine and hypotaurine on primary afferents are pharmacologically indistinguishable from the VR-DRP. These results are in agreement with the proposal that taurine or a taurine-like substance (possibly beta-alanine or hypotaurine) is the mediator of VR-DRP in amphibian spinal cord.
据报道,6-氨甲基-3-甲基-4H,1,2,4-苯并噻二嗪-1,1-二氧化物(AMBD,TAG)是中枢神经系统中牛磺酸和β-丙氨酸反应的特异性阻断剂。我们通过蔗糖间隙技术重新研究了AMBD对从离体半切青蛙脊髓记录的氨基酸和突触诱发反应的影响。当通过向正常林格溶液中添加河豚毒素(0.2 microM)或氯化锰(2 mM)来阻断间接反应时,AMBD(0.01 - 0.5 mM)选择性地拮抗牛磺酸、β-丙氨酸、次牛磺酸和曲酸胺在其髓内部分(背根终末,DRT)和背根神经节(DRG)诱发的初级传入纤维去极化,而对谷氨酸(在DRT上)、甘氨酸(在DRT上)或GABA(在DRT和DRG上)的反应没有显著影响。0.1 mM AMBD可使对牛磺酸和β-丙氨酸(1 mM)的去极化反应降低多达50%,而0.25 mM AMBD常常可完全拮抗。在正常林格溶液中,AMBD选择性地拮抗腹根刺激诱发的背根电位(VR-DRP,0.02 mM AMBD时出现阈值,0.25 mM时90%阻断);其他突触电位的持续时间和/或幅度增加,表明AMBD有强烈的惊厥作用。因此,牛磺酸、β-丙氨酸和次牛磺酸对初级传入纤维的去极化反应在药理学上与VR-DRP无法区分。这些结果与牛磺酸或类似牛磺酸的物质(可能是β-丙氨酸或次牛磺酸)是两栖动物脊髓中VR-DRP的介质这一观点一致。