ANP inhibits Na(+)-H+ antiport in proximal tubular brush border membrane: role of dopamine.
ANP inhibits Na(+)-H+ antiport in proximal tubular brush border membrane: role of dopamine.
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DOI：
10.1038/ki.1990.323
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发表时间：
1990-12
影响因子：
19.6
通讯作者：
Joseph Winaver;John C. Burnett;G. M. Tyce;T. Dousa
中科院分区：
文献类型：
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作者：
Joseph Winaver;John C. Burnett;G. M. Tyce;T. Dousa
ANP抑制近端肾小管刷状缘膜Na+-H+逆向转运：多巴胺的作用。2ANP对大鼠肾脏刷状缘膜泡(BBMV)的Na+-H+逆向转运和Na+-Pisymport有抑制作用(J Clin Invest75：1983)。在本研究中，我们研究了肾内注射心钠素引起近端肾小管转运系统改变的机制。与大鼠一样，给兔输注ANP导致利尿、钠尿和GFR增加；然而，与大鼠不同的是，磷酸盐排泄分数(PI)没有改变。在灌注心钠素的兔大脑皮层制备的BBMV中，Na+-H+反向转运率降低(Δ-27%)，但Na+依赖的PiP和L-Pro摄取与对照组无差异。体外培养的兔皮质小管悬液与心钠素10-7M共同孵育时，对肾小管上皮细胞Na~+-H~+反向转运无明显抑制作用，而与其他激素剂1U/mlPTH(Δ61%)或多巴胺(DA)10~(-4)M(Δ-34%)共同孵育，则对同一肾小管上皮细胞Na~+-H~+反向转运有抑制作用。然而，当肾小管与(10-5M)DA共同孵育时，加入10-7M心钠素确实使BBMV的Na+-H+逆向转运蛋白活性显著降低(Δ-21%)。相反，当PTH的抑制剂量低于最大值时，ANP没有表现出类似的抑制作用。为探讨心钠素是否可能通过多巴胺间接作用于体内近端小管，我们观察了心钠素对儿茶酚胺系统部分参数的影响。心钠素可显著增加(Δ+134%)尿中非结合型DA的排泄，提示肾内DA生成增加，但对血浆DA及其前体L-多巴和肾皮质组织提取物中DA含量无明显影响。综上所述，这些观察结果支持了循环ANP可抑制跨肾小管Na+-H+交换速率的假说：a)通过肾近端小管自分泌DA系统，即ANP，间接地促进肾内DA的产生，进而抑制Na+-H+逆向转运；b)此外，ANP还可能直接增强DA对Na+-H+逆向转运的抑制作用。
ANP inhibits Na+-H+antiport in proximal tubular brush border membrane: Role of dopamine.2Infusion of ANP to rats results in an inhibition of Na+-H+antiport and Na+-Pisymport in brush border membrane vesicles (BBMV) prepared from kidneys of these animals (J Clin Invest75:1983). iln the present study we investigated the intrarenal mechanism by which infused ANP elicits these changes in proximal tubular transport systems. As in rats, infusion of ANP to rabbits resulted in a diuresis, natriuresis, and increase in GFR; however, unlike in rats, the fractional excretion of phosphate (Pi) was not changed. In BBMV prepared from cortices of ANP-infused rabbits, the rate of Na+-H+antiport was decreased (Δ -27%), but Na+gradient-dependent uptakes of Piand L-proline were not different from controls. Incubation of rabbit cortical tubule suspension in vitro with ANP 10-7M alone had no inhibitory effect on Na+-H+antiport in BBMV prepared from these tubules, whereas incubation with other hormonal agents, 1 U/ml PTH (Δ 61%) or with dopamine (DA) 10-4M (Δ -34%), did inhibit the rate of Na+-H+antiport in BBMV from the same pool of tubules. However, when tubules were incubated in the presence of (10-5M) DA, the addition of 10-7M ANP did cause a significant (Δ -21%) decrease in Na+-H+antiport activity in BBMV. In contrast, ANP did not show similar inhibitory effect in the presence of submaximal inhibitory doses of PTH. To explore whether ANP may act on proximal tubules in vivo indirectly, via mediation of DA, we evaluated the effect of ANP on some parameters of catecholamine system in vivo. Infusion of ANP, in doses which caused inhibition of Na+-H+antiport in BBMV and natriuresis, markedly enhanced (Δ +134%) excretion of non-conjugated DA in urine, indicating increased intrarenal generation of DA, while it had no detectable effect on the plasma levels of DA, its precursor L-dopa, or on DA content in extracts of renal cortical tissue. Taken together, these observations provide evidence for the hypothesis that circulating ANP can inhibit the rate of Na+-H+exchange across renal BBM: a) indirectly, via the autocrine DA system in renal proximal tubules, that is, ANP, enhances the intrarenal generation of DA, which in turn inhibits Na+-H+antiport; b) in addition, ANP may also directly potentiate the inhibitory action of DA on Na+-H+antiport.