Clark M, Dar M S
Department of Pharmacology, School of Medicine East Carolina University, Greenville, NC 27858.
Pharmacol Biochem Behav. 1988 May;30(1):155-61. doi: 10.1016/0091-3057(88)90439-x.
The possible involvement of brain adenosine in acute ethanol-induced motor incoordination (MI) and inhibition of spontaneous motor activity (SMA) was investigated in male Sprague-Dawley rats. Pretreatment with theophylline or 7-(2-chloroethyl)-theophylline, adenosine antagonists, markedly reduced ethanol-induced MI and inhibition of SMA during a 60 min test period compared with saline + ethanol group. On the contrary, pretreatment with (-)-N6(R-phenylisopropyl)adenosine (R-PIA), an adenosine agonist, or dilazep, an adenosine uptake blocker, markedly potentiated the ethanol-induced MI as well as inhibition of SMA in a 60 min test period compared with saline + ethanol group. No effect on motor coordination was seen when the drug pretreatment was not followed by ethanol. However, the adenosine agonists and antagonists did alter SMA when the pretreatment with these drugs was not followed by ethanol. Ethanol clearance was not altered by the drug pretreatment as blood ethanol levels were similar in all groups except for lower ethanol levels in the R-PIA-treated group. Adenosine A1 binding studies, using 3H-R-PIA as the radioligand and crude membrane preparation from cerebellar cortex, revealed an increase in Bmax with no significant change in Kd in ethanol-treated animals vs. saline control. Theophylline pretreatment prevented the increase in Bmax elicited by ethanol. Collectively, the data suggest that endogenous cerebellar adenosine may be a participating factor in ethanol-induced motor dysfunctions.
在雄性Sprague-Dawley大鼠中研究了脑腺苷在急性乙醇诱导的运动不协调（MI）和自发运动活动（SMA）抑制中的可能作用。与生理盐水+乙醇组相比，用腺苷拮抗剂茶碱或7-（2-氯乙基）-茶碱预处理在60分钟的测试期内显著降低了乙醇诱导的MI和SMA抑制。相反，与生理盐水+乙醇组相比，用腺苷激动剂（-）-N6（R-苯异丙基）腺苷（R-PIA）或腺苷摄取阻滞剂双嘧达莫预处理在60分钟的测试期内显著增强了乙醇诱导的MI以及SMA抑制。当药物预处理后不给予乙醇时，未观察到对运动协调性的影响。然而，当这些药物预处理后不给予乙醇时，腺苷激动剂和拮抗剂确实改变了SMA。药物预处理未改变乙醇清除率，因为除R-PIA处理组乙醇水平较低外，所有组的血液乙醇水平相似。使用3H-R-PIA作为放射性配体和来自小脑皮质的粗膜制剂进行的腺苷A1结合研究显示，与生理盐水对照组相比，乙醇处理动物的Bmax增加，Kd无显著变化。茶碱预处理可防止乙醇引起的Bmax增加。总体而言，数据表明内源性小脑腺苷可能是乙醇诱导的运动功能障碍的一个参与因素。
