The 5HT1B receptor agonist, CP-93129, inhibits [3H]-GABA release from rat globus pallidus slices and reverses akinesia following intrapallidal injection in the reserpine-treated rat
The 5HT1B receptor agonist, CP-93129, inhibits [3H]-GABA release from rat globus pallidus slices and reverses akinesia following intrapallidal injection in the reserpine-treated rat
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DOI：
10.1038/sj.bjp.0703526
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发表时间：
2000-08-01
影响因子：
7.3
通讯作者：
Duty, S
中科院分区：
文献类型：
--
作者：
Chadha, A;Sur, C;Duty, S
1本研究检测了啮齿动物苍白球（GP）中5 HT（1B）受体的激活是否可以在体外减少GABA的释放，并在体内逆转利血平诱导的运动不能。2将雄性Sprague道利大鼠（300-350 g）的GP显微切片预先加入[H-3]-GABA。在随后的灌流期间，收集4分钟的级分用于释放分析。5 HT（1B）受体激动剂3-（1，2，5，6-四氢吡啶-4-基）吡咯并[3，2-B]吡啶-5-酮（CP-93129）对25 mM KCl诱发的释放的影响。3雄性Sprague道利大鼠（270-290 g），通过皮下注射利血平（5 mg kg（-1））使其运动不能。18小时后，检查单侧注射CP-93129诱导的旋转行为。4 CP-93129（0.6-16.2 μ M）对25 mM KCl诱发的[H-3]-GABA释放产生浓度依赖性抑制，最大抑制率为52.5 +/-4.5%。次最大浓度CP-93129的影响（5.4 μ M）被5 HT（1B）受体拮抗剂艾沙莫坦（10 μ M）完全抑制。5在苍白球内注射后，CP-93129（0.5 μ l中30-330 nmol）产生了剂量依赖性的净逆向旋转增加，最大值达到197 +/-在330 nmol.用艾沙莫坦（10 nmol/1 μ l）预处理可将次最大剂量CP-93129（220 nmol）的作用抑制84 +/-6%。6这些数据表明，至少有一些5 HT（1B）受体在GP中作为异源受体发挥作用，减少GABA的释放。此外，CP-93129介导的CP中这些受体的激活在利血平处理的PD大鼠模型中提供了运动不能的缓解。
1 This study examined whether activation of 5HT(1B) receptors in the rodent globus pallidus (GP) could reduce GABA release in vitro and reverse reserpine-induced akinesia in vivo.2 Microdissected slices of GP from male Sprague Dawley rats (300-350 g) were preloaded with [H-3]-GABA. During subsequent superfusion, 4 min fractions were collected for analysis of release. The effects of the 5HT(1B) receptor agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP-93129), on 25 mM KCl-evoked release were examined using a standard dual stimulation paradigm.3 Male Sprague Dawley rats (270-290 g), stereotaxically cannulated above the GP, were rendered akinetic by injection of reserpine (5 mg kg(-1) s.c.). Eighteen hours later, the rotational behaviour induced by unilateral injection of CP-93129 was examined.4 CP-93129 (0.6-16.2 mu M) produced a concentration-dependent inhibition of 25 mM KCl-evoked [H-3]-GABA release reaching a maximum inhibition of 52.5 +/- 4.5%. The effect of a submaximal concentration of CP-93129 (5.4 mu M) was fully inhibited by the 5HT(1B) receptor antagonist, isamoltane (10 mu M).5 Following intrapallidal injection, CP-93129 (30-330 nmol in 0.5 mu l) produced a dose-dependent increase in net contraversive rotations reaching a maximum of 197 +/- 32 rotations in 240 min at 330 nmol. Pre-treatment with isamoltane (10 nmol in 1 mu l) inhibited the effects of a submaximal dose of CP-93129 (220 nmol) by 84 +/- 6%.6 These data suggest that at least some 5HT(1B) receptor function as heteroreceptors in the GP, reducing the release of GABA. Moreover, CP-93129-mediated activation of these receptors in the CP provides relief of akinesia in the reserpine-treated rat model of PD.