多巴胺 D2L 受体刺激小鼠 LTK- 细胞中的 Na+/K(+)-ATP 酶活性。

Dopamine D2L receptors stimulate Na+/K(+)-ATPase activity in murine LTK- cells.

作者信息

Yamaguchi I, Walk S F, Jose P A, Felder R A

机构信息

Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.

出版信息

Mol Pharmacol. 1996 Feb;49(2):373-8.

PMID:8632772

Abstract

Ion transport can be regulated by dopamine receptors. D1-like receptors inhibit both Na+/H+ exchange (NHE) and Na+/K(+)-ATPase activity, whereas D2-like receptors stimulate NHE. However, the effect of D2-like receptors on Na+/K(+)-ATPase activity is controversial. In renal proximal tubular cells, where several D1-like and D2-like receptors are expressed, D2 agonists have been reported either to have no effect or to act in concert with D1 agonists to inhibit Na+/K(+)-ATPase activity. We therefore studied the effect of D2 receptors on Na+/K(+)-ATPase activity in LTK- cells transfected with a rat D2Long receptor cDNA (maximum receptor density = 0.91 +/- 0.26 pmol/mg protein, dissociation constant = 2.39 +/- 0.79 nM, seven experiments). The activation of D2 receptors in these transfected cells by the selective D2 agonist LY171555 led to the inhibition of forskolin-stimulated cAMP accumulation. In the D2Long-transfected, but not in nontransfected cells, LY171555 caused a concentration-dependent stimulation of Na+/K(+)-ATPase activity (EC50 = 0.55 +/- 0.2 microM, Emax = 28 +/- 6%, six experiments), which was completely blocked by the D2-selective antagonist (-)-sulpiride. The D2-stimulated Na+/K(+)-ATPase activity was not secondary to D2 receptor activation of K+ channels or NHE activity since LY171555 stimulated Na+/K(+)-ATPase activity in D2Long-transfected cells, even when K+ channels were blocked by CsCl and intracellular Na+ was clamped by monensin. The D2-stimulated Na+/K(+)-ATPase activity was blocked by pertussis toxin and mimicked by dideoxyadenosine. We conclude that agonist occupancy of D2Long dopamine receptors stimulates Na+/K(+)-ATPase activity; this effect is mediated by the inhibition of cAMP production and is independent of intracellular Na+ and K+ concentration.

摘要

离子转运可受多巴胺受体调节。D1样受体抑制Na⁺/H⁺交换（NHE）和Na⁺/K⁺-ATP酶活性，而D2样受体则刺激NHE。然而，D2样受体对Na⁺/K⁺-ATP酶活性的影响存在争议。在表达多种D1样和D2样受体的肾近端小管细胞中，有报道称D2激动剂要么无作用，要么与D1激动剂协同作用以抑制Na⁺/K⁺-ATP酶活性。因此，我们研究了D2受体对转染大鼠D2Long受体cDNA的LTK⁻细胞中Na⁺/K⁺-ATP酶活性的影响（最大受体密度 = 0.91±0.26 pmol/mg蛋白，解离常数 = 2.39±0.79 nM，七个实验）。选择性D2激动剂LY171555激活这些转染细胞中的D2受体，导致福斯可林刺激的cAMP积累受到抑制。在转染D2Long的细胞中，而非未转染的细胞中，LY171555引起Na⁺/K⁺-ATP酶活性的浓度依赖性刺激（EC50 = 0.55±0.2 μM，Emax = 28±6%，六个实验），这被D2选择性拮抗剂（-）-舒必利完全阻断。D2刺激的Na⁺/K⁺-ATP酶活性并非继发于D₂受体对钾通道或NHE活性的激活，因为即使钾通道被氯化铯阻断且细胞内钠被莫能菌素钳制，LY171555仍能刺激转染D2Long的细胞中的Na⁺/K⁺-ATP酶活性。D2刺激的Na⁺/K⁺-ATP酶活性被百日咳毒素阻断，并被双脱氧腺苷模拟。我们得出结论，D2Long多巴胺受体的激动剂占据可刺激Na⁺/K⁺-ATP酶活性；这种作用是通过抑制cAMP产生介导的，且独立于细胞内钠和钾浓度。