Quik M, Iversen L L
Naunyn Schmiedebergs Arch Pharmacol. 1978 Sep;304(2):141-5. doi: 10.1007/BF00495550.
Repeated daily administration of the dopamine (DA) agonist bromocriptine (15 mg/kg; s.cut.) to rats led to a time dependent decrease in the in vitro binding of [3H]spiperone to striatal membranes. Kinetic analysis of [3H]spiperone binding after 2 and 7 days of bromocriptine treatment showed a 25-50% reduction in the total number of binding sites with no changein their affinity for spiperone. There was also a decreased accumulation of cyclic AMP (cAMP) in striatal slices in response to DA after bromocriptine treatment. The DA-sensitive adenylate cyclase in striatal homogenates, however, remained unchanged in bromocriptine treated rats. There was also no change in cyclic nucleotide phosphodiesterase activity in striatal tissue after bromocriptine treatment. Furthermore, incubation of striatal slices in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine did not alter the decreased cAMP response to DA after 2 days of bromocriptine treatment. These results suggest that a decreased number of DA receptor sites may be responsible for the reduced cAMP response to DA in striatal slices after bromocriptine treatment.
每天对大鼠重复皮下注射多巴胺（DA）激动剂溴隐亭（15毫克/千克），会导致[3H]螺哌隆与纹状体膜的体外结合随时间下降。对溴隐亭治疗2天和7天后的[3H]螺哌隆结合进行动力学分析表明，结合位点总数减少了25 - 50%，而它们对螺哌隆的亲和力没有变化。溴隐亭治疗后，纹状体切片中对DA反应的环磷酸腺苷（cAMP）积累也减少。然而，溴隐亭治疗的大鼠纹状体匀浆中对DA敏感的腺苷酸环化酶保持不变。溴隐亭治疗后纹状体组织中的环核苷酸磷酸二酯酶活性也没有变化。此外，在磷酸二酯酶抑制剂异丁基甲基黄嘌呤存在的情况下孵育纹状体切片，在溴隐亭治疗2天后，对DA的cAMP反应降低没有改变。这些结果表明，DA受体位点数量减少可能是溴隐亭治疗后纹状体切片中对DA的cAMP反应降低的原因。
