Bertorello A, Aperia A
Department of Pediatrics, Karolinska Institute, St. Göran's Children's Hospital, Stockholm, Sweden.
Am J Physiol. 1989 Feb;256(2 Pt 2):F370-3. doi: 10.1152/ajprenal.1989.256.2.F370.
Activators of protein kinase C (PKC) inhibit sodium transport in proximal tubules (PT) (M. Baum and S. R. Hays. Am. J. Physiol. 254 (Renal Fluid Electrolyte Physiol. 23): F9-F14, 1988. In this study we have evaluated the effect of PKC activators on the enzyme responsible for active sodium transport, Na+-K+-ATPase. Both endogenous (diacylglycerol, DAG) and exogenous (phorbol esters, PE) activators were used. Enzyme activity was determined in permeabilized single PT segments. In vehicle-incubated PT, Na+-K+-ATPase activity (pmol Pi.mm tubule-1.-1 h) was 1,403 +/- 128. The synthetic DAG, L-alpha-l-oleoyl-2-acetoyl-sn-3-glycerol (10(-4) M) significantly inhibited Na+-K+-ATPase activity to 673 +/- 51, P less than 0.05. The PE-phorbol 12,13-dibutyrate (PDBu), induced a time- and dose-dependent inhibition of Na+-K+-ATPase activity. Inhibition was significant at 15 and maximal at 20 min. Na+-K+-ATPase activity in PT incubated with PDBu was 796 +/- 171 (10(-8) M), 570 +/- 198 (10(-7) M), and 484 +/- 130 (10(-6) M). A PE that does not activate PKC, 4-alpha-phorbol didecanoate, did not inhibit Na+-K+-ATPase activity. PDBu 10(-7) M had no effect on purified Na+-K+-ATPase. Sphingosine (SP), a PKC inhibitor, abolished the inhibitory effect of PDBu (10(-7) M) on Na+-K+-ATPase activity. Dopamine (DA) is a physiological inhibitor of Na+-K+-ATPase activity in PT [A. Bertorello, T. Hökfelt, M. Goldstein, and A. Aperia Am. J. Physiol. 254(Renal Fluid Electrolyte Physiol. 23): F795-F801, 1988].(ABSTRACT TRUNCATED AT 250 WORDS)
蛋白激酶C（PKC）激活剂可抑制近端小管（PT）中的钠转运（M. 鲍姆和S. R. 海斯。《美国生理学杂志》254卷（肾流体电解质生理学23）：F9 - F14，1988年。在本研究中，我们评估了PKC激活剂对负责主动钠转运的酶——钠钾ATP酶的作用。使用了内源性（二酰基甘油，DAG）和外源性（佛波酯，PE）激活剂。在通透的单个PT节段中测定酶活性。在载体孵育的PT中，钠钾ATP酶活性（pmol Pi·mm小管⁻¹·h⁻¹）为1403±128。合成的DAG，L-α-1-油酰基-2-乙酰基-sn-3-甘油（10⁻⁴ M）显著抑制钠钾ATP酶活性至673±51，P<0.05。PE-佛波醇12,13-二丁酸酯（PDBu）诱导钠钾ATP酶活性出现时间和剂量依赖性抑制。在15分钟时抑制显著，20分钟时达到最大抑制。与PDBu孵育的PT中的钠钾ATP酶活性分别为796±171（10⁻⁸ M）、570±198（10⁻⁷ M）和484±130（10⁻⁶ M）。一种不激活PKC的PE，4-α-佛波醇二癸酸酯，不抑制钠钾ATP酶活性。10⁻⁷ M的PDBu对纯化的钠钾ATP酶无作用。鞘氨醇（SP），一种PKC抑制剂，消除了PDBu（10⁻⁷ M）对钠钾ATP酶活性的抑制作用。多巴胺（DA）是PT中钠钾ATP酶活性的生理性抑制剂[A. 贝托雷洛、T. 赫克费尔特、M. 戈尔茨坦和A. 阿佩里亚。《美国生理学杂志》254卷（肾流体电解质生理学23）：F795 - F801，1988年]。（摘要截断于250字）
