Tomiyama K, Noguchi M, Koshikawa N, Kobayashi M
Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan.
J Neurochem. 1993 May;60(5):1690-5. doi: 10.1111/j.1471-4159.1993.tb13392.x.
The effects of the selective dopamine D2 receptor antagonists YM-09151-2 and l-sulpiride on the in vivo release of dopamine (DA), L-3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in rat striatum were investigated. The drugs were injected into the striatum through a microinjection needle attached to a dialysis probe. YM-09151-2 (0.1 or 1.0 microgram/0.5 microliter) injected into the striatum produced a dramatic rapid-onset transient increase in striatal DA release in a dose-dependent manner. However, the DA increase induced by l-sulpiride (15 or 75 ng/0.5 microliter) was small and of slower onset. An increase of DOPAC levels by YM-09151-2 was biphasic: The first peak occurred at 40 min, followed by a delayed-onset gradual increase. Slower-onset gradual increases were also found in DOPAC levels after l-sulpiride injection and in HVA levels after injections of both YM-09151-2 and l-sulpiride. The infusion of tetrodotoxin (TTX; 2 microM) revealed two different types of DA release mechanisms: The rapid-onset transient DA release induced by YM-09151-2 was TTX insensitive, whereas the slower-onset DA release induced by l-sulpiride was TTX sensitive. Moreover, the rapid-onset transient DA release was Ca2+ independent and was not affected by pretreatment with l-sulpiride or nomifensine. Therefore, it is concluded that YM-09151-2 injected into the striatum produced a transient striatal DA release that is independent of D2 receptors and the action potential.
研究了选择性多巴胺D2受体拮抗剂YM-09151-2和左旋舒必利对大鼠纹状体中多巴胺（DA）、L-3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）体内释放的影响。通过连接到透析探针的微量注射针将药物注入纹状体。注入纹状体的YM-09151-2（0.1或1.0微克/0.5微升）以剂量依赖的方式引起纹状体DA释放急剧快速起始的短暂增加。然而，左旋舒必利（15或75纳克/0.5微升）引起的DA增加较小且起始较慢。YM-09151-2使DOPAC水平升高呈双相性：第一个峰值出现在40分钟，随后是延迟起始的逐渐增加。左旋舒必利注射后DOPAC水平以及YM-09151-2和左旋舒必利注射后HVA水平也出现起始较慢的逐渐增加。注入河豚毒素（TTX；2微摩尔）揭示了两种不同类型的DA释放机制：YM-09151-2诱导的快速起始短暂DA释放对TTX不敏感，而左旋舒必利诱导的起始较慢的DA释放对TTX敏感。此外，快速起始短暂DA释放不依赖Ca2+，且不受左旋舒必利或诺米芬预处理的影响。因此，得出结论，注入纹状体的YM-09151-2产生了与D2受体和动作电位无关的短暂纹状体DA释放。
