Tanaka T, Yoshida M, Yokoo H, Mizoguchi K, Tanaka M
Department of Pharmacology, Kurume University School of Medicine, Japan.
Pharmacol Biochem Behav. 1995 Dec;52(4):831-5. doi: 10.1016/0091-3057(95)00151-l.
We used in vivo brain microdialysis to investigate the role of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in dopamine (DA) release regulated by DA autoreceptors in the rat striatum. Local infusions of the KATP channel opener nicorandil (10(-5)-10(-3) M) into the striatum through the dialysis membrane produced dose-dependent decreases in extracellular concentrations of DA. Local application of the D2 receptor antagonist (-)-sulpiride (SLP, 10(-5) M) or the KATP channel blocker quinine (QIN, 10(-3) M) produced significant increases in extracellular concentrations of DA. Nicorandil (10(-3) M) significantly blocked SLP (10(-5) M)- or QIN (10(-3) M)-induced increases in DA levels in the striatum. These results suggest that activation or inhibition of the KATP channel in the striatum causes decreases or increases, respectively, in endogenous DA release in vivo. Furthermore, SLP-induced increases in DA levels caused by blocking the tonic activation of DA autoreceptors are inhibited by the activation of KATP channels. These data suggest that striatal DA autoreceptors may inhibit DA release tonically by activating the KATP channel.
我们采用体内脑微透析技术,研究三磷酸腺苷(ATP)敏感性钾(KATP)通道在大鼠纹状体中多巴胺(DA)自身受体调节DA释放过程中的作用。通过透析膜向纹状体局部注入KATP通道开放剂尼可地尔(10^(-5)-10^(-3) M),可使细胞外DA浓度呈剂量依赖性降低。局部应用D2受体拮抗剂(-)-舒必利(SLP,10^(-5) M)或KATP通道阻滞剂奎宁(QIN,10^(-3) M),可使细胞外DA浓度显著升高。尼可地尔(10^(-3) M)可显著阻断SLP(10^(-5) M)或QIN(10^(-3) M)诱导的纹状体DA水平升高。这些结果表明,纹状体中KATP通道的激活或抑制分别导致体内内源性DA释放减少或增加。此外,通过阻断DA自身受体的紧张性激活而引起的SLP诱导的DA水平升高,会被KATP通道的激活所抑制。这些数据表明,纹状体DA自身受体可能通过激活KATP通道来紧张性抑制DA释放。