Altar C A, Boyar W C, Kim H S
Research Department, Ciba-Geigy Corporation, Summit, NJ 07901.
Eur J Pharmacol. 1990 May 31;181(1-2):17-21. doi: 10.1016/0014-2999(90)90240-7.
The D1 and D2 subtypes of the dopamine receptor have been distinguished by their opposing effects on levels of neostriatal cyclic adenosine monophosphate (cAMP). The studies reported here show that the content of cyclic guanosine monophosphate (cGMP) in the mouse neostriatum is modulated by dopaminergic drugs in a manner which also discriminates D1 and D2 receptors. D1 receptor stimulation with SKF 38393 produced up to 90%, dose-related increases in neostriatal cGMP, whereas D1 antagonism with SCH 23390 decreased cGMP by 30% and blocked the increase induced by SKF 38393. D2 receptor stimulation with quinpirole did not alter cGMP levels whereas D2 antagonism increased cGMP by 40-60% after haloperidol and by up to 100% after sulpiride. The increases in neostriatal cGMP levels following D1 agonism were potentiated in an additive manner by haloperidol. Thus, neostriatal cGMP content is positively controlled by D1 agonism and negatively controlled by or unlinked to the D2 receptor. The reciprocal control of neostriatal cGMP levels by D1- and D2-selective compounds may contribute to the separate as well as combined actions of D1 and D2 ligands.
多巴胺受体的D1和D2亚型可通过它们对新纹状体环磷酸腺苷（cAMP）水平的相反作用来区分。本文报道的研究表明，小鼠新纹状体中环磷酸鸟苷（cGMP）的含量受多巴胺能药物的调节，这种调节方式也能区分D1和D2受体。用SKF 38393刺激D1受体可使新纹状体cGMP含量增加高达90%，且呈剂量相关性，而用SCH 23390拮抗D1受体可使cGMP含量降低30%，并阻断SKF 38393诱导的增加。用喹吡罗刺激D2受体不会改变cGMP水平，而拮抗D2受体后，氟哌啶醇可使cGMP含量增加40 - 60%，舒必利可使其增加高达100%。氟哌啶醇以相加的方式增强了D1激动剂作用后新纹状体cGMP水平的升高。因此，新纹状体cGMP含量受D1激动剂正向调控，受D2受体负向调控或与之无关。D1和D2选择性化合物对新纹状体cGMP水平的相互调控可能有助于D1和D2配体的单独作用以及联合作用。
