多巴胺对大鼠纹状体突触前和突触后膜 Na+,K+-ATP 酶活性调节的差异

用蔗糖-Ficol梯度不连续离心法制备大鼠纹状体突触前膜和突触后膜,研究多巴胺(DA)受体对突触前和突触后膜Na⁺,K⁺-ATP酶活性的调节作用。结果表明,DA(10^-8～10^-5mol·L^-1)显著抑制突触后膜Na⁺,K⁺-ATP酶的活性,单独用选择性D1(SKF38393)或D2(LY171555)受体激动剂均无抑制作用,而当二者合用时则产生与DA相似的抑制效应。DA对Na⁺,K⁺-ATP酶的抑制效应可被单独用选择性D1(SCH23390)或D2(spiperone)受体拮抗剂而逆转。相反,DA却能显著激活突触前膜Na⁺,K⁺-ATP酶的活性,单用spiperone即可逆转此激活效应。结果提示,突触前和突触后DA受体对Na⁺,K⁺-ATP酶的调节存在差异,可能与它们的不同生理功能有关。

DIFFERENTIAL REGULATION OF DOPAMINE PECEPTORS ON PRE-AND POSTSYNAPTIC Na+,K+-ATPase IN PAT STRIATUM

The pre- and postsynaptic membranes isolated from rat striatum were used to investigate the regulation of dopamine receptors on striatal Na+, K(+)-ATPase in these membranes. The activity of Na+, K(+)-ATPase was determined by colorimetric method. Dopamine (DA) was found to inhibit the Na+, K(+)-ATPase activity on postsynaptic membranes in a concentration-dependent manner with a IC50 value of 4.6 mumol.L-1. This inhibitory effect was reversed by either selective D1 receptor antagonist SCH23390 or selective D2 receptor antagonist spipernone. The inhibitory effect similar to DA was produced by combination with selective D1 receptor agonist SKF38393 and selective D2 receptor agonist LY171555. In contrast, under the same experimental conditions, DA (10(-8)-10(-5) mol.L-1) was shown to activate the activity of Na+, K(+)-ATPase on presynaptic membranes in a concentration-dependent manner. Meanwhile, the stimulatory effect was reversed by spiperone alone rather than by SCH23390. These results show the differential regulation of presytnaptic and postsynaptic DA receptors on Na+, K(+)-ATPase in rat striatum.