Severson J A, Randall P K, Wilcox R E
Department of Psychiatry, School of Medicine, University of Southern California, Los Angeles 90033.
Eur J Pharmacol. 1990 Apr 25;188(4-5):283-6. doi: 10.1016/0922-4106(90)90013-n.
The formation of a ternary complex of agonist, receptor, and G-protein precedes inhibition of adenylate cyclase and is associated with high-affinity agonist binding. The present experiment was conducted to determine if a single direct dopamine (DA) agonist, apomorphine (APO), pretreatment could produce a rapid uncoupling of the striatal DA D-2 receptor from its G-proteins. APO (30 mg/kg, i.p.) and saline were administered once, with killing 60 or 90 min following the APO or vehicle treatment. APO pretreatment resulted in a reduction in the high-affinity binding of DA to the striatal DA D-2 receptor without altering total agonist binding. The total density of antagonist-defined D-2 receptors (Bmax) was not altered by the treatment. The present results represent, to our knowledge, the first demonstration of changes in high-affinity agonist binding to the DA D-2 receptor following a single in vivo pretreatment of a direct DA agonist.
激动剂、受体和G蛋白三元复合物的形成先于腺苷酸环化酶的抑制，且与高亲和力激动剂结合相关。进行本实验以确定单次直接多巴胺（DA）激动剂阿扑吗啡（APO）预处理是否能使纹状体DA D-2受体与其G蛋白快速解偶联。腹腔注射APO（30 mg/kg）和生理盐水一次，在APO或赋形剂处理后60或90分钟处死动物。APO预处理导致DA与纹状体DA D-2受体的高亲和力结合减少，而不改变总激动剂结合。拮抗剂定义的D-2受体的总密度（Bmax）不受该处理影响。据我们所知，本研究结果首次证明了单次体内直接DA激动剂预处理后，高亲和力激动剂与DA D-2受体结合的变化。
