Bertorello A, Aperia A
Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institute, Stockholm, Sweden.
Am J Physiol. 1990 Dec;259(6 Pt 2):F924-8. doi: 10.1152/ajprenal.1990.259.6.F924.
This study examines the receptor mechanisms by which dopamine (DA) inhibits Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in single permeabilized proximal tubule (PCT). Na(+)-K(+)-ATPase activity was inhibited in the presence of both DA1- and DA2-specific agonists but not by either agonist alone. The inhibition induced by DA (10(-6) M) was attenuated in the presence of either of the two DA2-specific antagonists S-sulpiride and YM 09151 at 10(-5) M and in the presence of the DA1 antagonist SCH 23390 (10(-5) M). PCT adenosine 3',5'-cyclic monophosphate (cAMP) levels were significantly increased in the presence of DA and DA1 agonist, but DA2 agonist had no effect on cell cAMP levels. Na(+)-K(+)-ATPase activity was significantly inhibited in PCT incubated with DA2 agonist (10(-5) M) and dibutyryl (DB)-cAMP (10(-6) M) but not with DA2 agonist (10(-5) M) only. PCT Na(+)-K(+)-ATPase activity was also significantly inhibited in the presence of both DA2 agonist (10(-5) M) and forskolin (10(-6) M). Neither DBcAMP (10(-6) M) nor forskolin (10(-6) M) alone inhibited Na(+)-K(+)-ATPase activity. In tubules incubated with DA (10(-8) to 10(-9) M), the presence of DBcAMP (10(-6) M) enhanced the sensitivity by which DA inhibited Na(+)-K(+)-ATPase activity. We conclude that PCT Na(+)-K(+)-ATPase activity is inhibited by a synergistic action of the DA1 and DA2 receptors, with the DA1 receptor acting to increase cell cAMP levels.
本研究探讨多巴胺（DA）抑制单个透化近端小管（PCT）中钠钾腺苷三磷酸酶（ATP酶）活性的受体机制。在DA1和DA2特异性激动剂同时存在时，钠钾ATP酶活性受到抑制，但单独使用任何一种激动剂时均无此作用。DA（10⁻⁶ M）诱导的抑制作用在10⁻⁵ M的两种DA2特异性拮抗剂S-舒必利和YM 09151之一存在时以及在DA1拮抗剂SCH 23390（10⁻⁵ M）存在时减弱。在DA和DA1激动剂存在时，PCT腺苷3',5'-环磷酸（cAMP）水平显著升高，但DA2激动剂对细胞cAMP水平无影响。用DA2激动剂（10⁻⁵ M）和二丁酰（DB）-cAMP（10⁻⁶ M）孵育的PCT中，钠钾ATP酶活性显著受到抑制，但仅用DA2激动剂（10⁻⁵ M）时则无此现象。在DA2激动剂（10⁻⁵ M）和福斯高林（10⁻⁶ M）同时存在时，PCT钠钾ATP酶活性也显著受到抑制。单独的DBcAMP（10⁻⁶ M）和福斯高林（10⁻⁶ M）均不抑制钠钾ATP酶活性。在用DA（10⁻⁸至10⁻⁹ M）孵育的小管中，DBcAMP（10⁻⁶ M）的存在增强了DA抑制钠钾ATP酶活性的敏感性。我们得出结论，PCT钠钾ATP酶活性受到DA1和DA2受体的协同作用抑制，其中DA1受体作用是增加细胞cAMP水平。
