Dar M S, Clark M
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
Alcohol Clin Exp Res. 1992 Dec;16(6):1138-46. doi: 10.1111/j.1530-0277.1992.tb00710.x.
Our previously published reports have provided data that have supported a functional correlation between ethanol-induced changes in the characteristics of adenosine receptor, adenosine uptake and release in the brain, and ethanol-induced motor incoordination. The present data demonstrated a cross-tolerance between ethanol and adenosine further supporting the hypothesis that brain adenosine modulates the motor impairing effects of ethanol. Mice that received (-)-N6-cyclohexyladenosine (CHA) [0.25 mg/kg/day, intraperitoneally (ip)] for 10 days exhibited marked attenuation (cross-tolerance) to acute ethanol-induced motor incoordination compared with chronic saline (ip) controls. The attenuation of acute ethanol-induced motor incoordination was essentially same in animals that received CHA (25 ng/5 microliters/day for 10 days) by the intracerebroventricular (icv) route as opposed to the controls that chronically received artificial cerebral spinal fluid by the same route. Similarly, tolerance was exhibited to acute CHA (0.125 mg/kg ip and 12.5 ng/5 microliters icv) by animals fed liquid ethanol (19.5 g/kg/24 hr) for 10 days compared with none in the pair-fed sucrose controls. Scatchard plots using cerebellar tissue homogenates from animals given chronic CHA or chronic ethanol indicated no change in Bmax and/or Kd values for CHA binding when compared with CHA binding in tissues from their respective controls. However, a lack of any change in the binding characteristics cannot rule out the involvement of adenosine receptors in the observed cross-tolerance between ethanol and CHA. The results may suggest desensitization of adenosine A1 receptors due to chronic CHA and ethanol as an alternate possible explanation in the development of cross-tolerance between adenosine (CHA) and ethanol.
我们之前发表的报告提供的数据支持了乙醇诱导的大脑中腺苷受体特性变化、腺苷摄取与释放以及乙醇诱导的运动不协调之间的功能相关性。目前的数据表明乙醇与腺苷之间存在交叉耐受性，进一步支持了大脑腺苷调节乙醇运动损害作用的假说。接受（-）-N6-环己基腺苷（CHA）[0.25毫克/千克/天，腹腔注射（ip）]10天的小鼠，与慢性生理盐水（ip）对照相比，对急性乙醇诱导的运动不协调表现出明显的减弱（交叉耐受性）。通过脑室内（icv）途径接受CHA（25纳克/5微升/天，持续10天）的动物，其急性乙醇诱导的运动不协调的减弱程度与通过相同途径长期接受人工脑脊液的对照动物基本相同。同样，与成对喂食蔗糖的对照动物相比，喂食液态乙醇（19.5克/千克/24小时）10天的动物对急性CHA（0.125毫克/千克ip和12.5纳克/5微升icv）也表现出耐受性。使用来自给予慢性CHA或慢性乙醇的动物的小脑组织匀浆进行的Scatchard作图表明，与各自对照组织中的CHA结合相比，CHA结合的Bmax和/或Kd值没有变化。然而，结合特性没有任何变化并不能排除腺苷受体参与乙醇和CHA之间观察到的交叉耐受性。结果可能表明，由于慢性CHA和乙醇导致腺苷A1受体脱敏，这是腺苷（CHA）和乙醇之间交叉耐受性发展的另一种可能解释。
