Kamisaki Y, Hamahashi T, Okada C M, Itoh T
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Brain Res. 1991 Dec 24;568(1-2):193-8. doi: 10.1016/0006-8993(91)91397-j.
Release of endogenous glutamic acid (Glu), aspartic acid (Asp) and gamma-aminobutyric acid (GABA) has been investigated using synaptosomes prepared from rat cerebral cortex. Exposure in superfusion to a depolarizing concentration of KCl (30 mM) evoked 3-, 2- and 2-fold increases in Glu, Asp and GABA release, respectively. More than 70% of Glu and Asp overflow were calcium-dependent, although 67% of the GABA overflow was calcium-independent. Clonidine inhibited the K(+)-evoked overflow of Glu and Asp in a concentration-dependent manner, but the GABA overflow was not inhibited. Clonidine inhibited K(+)-evoked Glu and Asp overflow to 40 and 30% of the control with a potency (IC50) of 11 and 36 nM, respectively. Similarly, norepinephrine inhibited the K(+)-evoked overflow of Glu and Asp, although phenylephrine and isoproterenol showed no effect. Rauwolscine, yohimbine and idazoxan counteracted the effects of clonidine on Glu and Asp overflow. The data suggest that the depolarization-evoked overflow of excitatory amino acids is regulated in an inhibitory fashion by alpha 2 adrenoceptors, which are located on the nerve terminals of Glu and Asp neurons in rat cortex.
利用从大鼠大脑皮层制备的突触体，对内源性谷氨酸（Glu）、天冬氨酸（Asp）和γ-氨基丁酸（GABA）的释放进行了研究。在灌流中暴露于去极化浓度的氯化钾（30 mM）分别引起Glu、Asp和GABA释放增加3倍、2倍和2倍。超过70%的Glu和Asp溢出是钙依赖性的，尽管67%的GABA溢出是钙非依赖性的。可乐定以浓度依赖性方式抑制K⁺诱发的Glu和Asp溢出，但不抑制GABA溢出。可乐定将K⁺诱发的Glu和Asp溢出分别抑制至对照的40%和30%，其效力（IC50）分别为11和36 nM。同样，去甲肾上腺素抑制K⁺诱发的Glu和Asp溢出，而苯肾上腺素和异丙肾上腺素则无作用。育亨宾、利血平与咪唑克生可抵消可乐定对Glu和Asp溢出的作用。数据表明，去极化诱发的兴奋性氨基酸溢出受到α₂肾上腺素能受体的抑制性调节，这些受体位于大鼠皮层Glu和Asp神经元的神经末梢上。
