PROSTAGLANDIN-E2 INHIBITS SODIUM-TRANSPORT IN RABBIT CORTICAL COLLECTING DUCT BY INCREASING INTRACELLULAR CALCIUM
PROSTAGLANDIN-E2 INHIBITS SODIUM-TRANSPORT IN RABBIT CORTICAL COLLECTING DUCT BY INCREASING INTRACELLULAR CALCIUM
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DOI：
10.1172/jci115227
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发表时间：
1991-06-01
影响因子：
15.9
通讯作者：
BREYER, MD
中科院分区：
文献类型：
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作者：
HEBERT, RL;JACOBSON, HR;BREYER, MD
本文探讨了前列腺素E_2（PGE_2）抑制家兔皮质集合管（CCD）钠吸收（J（Na））的机制。 PGE 2激活CCD中至少三种信号传导机制：（a）PGE 2本身增加cAMP生成（B）PGE 2还抑制加压素刺激的cAMP积累，和（c）PGE 2升高细胞内钙（[Ca++]i）。 我们测试了这些信号通路对PGE 2对Na+吸收的作用的贡献，测量了微灌注兔CCD中的Na-22通量（J（Na））和[Ca++]i（使用fura-2）。 在对照研究中，PGE 2将J（Na）从28.2 +/- 3.4降至15.6 +/- 2.6 pmol.mm-1.min-1。 将浴钙从2.4 nM降低至45 nM本身不会改变J（Na），但在这种情况下，PGE 2未能抑制J（Na）（28.6 +/- 5.4至38.5 +/- 4.0）。 在单独的小管中，PGE 2以穗状方式升高[Ca++]i，然后持续升高。 然而，在45 nM浴Ca++中，PGE 2未能产生持续的[Ca++]i升高。 虽然用百日咳毒素预处理CCD阻断了PGE 2对加压素刺激的水渗透性的抑制，但它并没有阻断PGE 2对J（Na）的作用。 为了观察cAMP的产生是否有助于PGE 2对J（Na）的作用，我们测试了外源性cAMP（8-氯苯硫基（CPT）cAMP）对J（Na）的作用。0.1 mM 8-CPTcAMP将J（Na）从35.75 +/- 2.3降低至21.6 +/- 2.2。 然而，加入PGE 2进一步使J（Na）钝化至15.9 +/-1.3。 在用吲哚美辛预处理的CCD中，8-CPTcAMP没有显著降低J（Na）33.6 +/- 2.8 vs. 28.4 +/- 2。 然而，叠加的PGE 2将J（Na）降低至19.0 +/-3.0。 我们的结论是，前列腺素E2抑制钠转运主要是通过增加细胞内钙。 这种作用不是由百日咳毒素敏感的G蛋白介导的。 最后，cAMP，通过环加氧酶依赖性机制，也抑制CCD J（Na），并可能有助于PGE 2对J（Na）在兔CCD的影响。
The mechanism by which prostaglandin E2 (PGE2) inhibits sodium absorption (J(Na)) in the rabbit cortical collecting duct (CCD) was explored. PGE2 activates at least three signaling mechanisms in the CCD: (a) by itself PGE2 increases cAMP generation (b) PGE2 also inhibits vasopressin-stimulated cAMP accumulation, and (c) PGE2 raises intracellular calcium ([Ca++]i). We tested the contribution of these signaling pathways to PGE2's effect on Na+ absorption, measuring Na-22 flux (J(Na)) and [Ca++]i (using fura-2) in microperfused rabbit CCDs. In control studies PGE2 reduced J(Na) from 28.2 +/- 3.4 to 15.6 +/- 2.6 pmol.mm-1.min-1. Lowering bath calcium from 2.4 to 45 nM did not by itself alter J(Na) but in this setting PGE2 failed to inhibit J(Na) (28.6 +/- 5.4 to 38.5 +/- 4.0). In separate tubules, PGE2 raised [Ca++]i in a spike-like fashion followed by a sustained elevation. However, in 45 nM bath Ca++, PGE2 failed to produce a sustained [Ca++]i elevation. While pretreatment of CCDs with pertussis toxin blocked PGE2 inhibition of vasopressin-stimulated water permeability, it did not block the effect of PGE2 on J(Na). To see if cAMP generation contributes to the effect of PGE2 on J(Na), we tested the effect of exogenous cAMP, (8-chlorophenylthio(CPT)cAMP) on J(Na). 0.1 mM 8-CPTcAMP reduced J(Na) from 35.75 +/- 2.3 to 21.6 +/- 2.2. However, the addition of PGE2 further blunted J(Na) to 15.9 +/- 1.3. In CCDs pretreated with indomethacin, 8-CPTcAMP did not significantly decrease J(Na) 33.6 +/- 2.8 vs. 28.4 +/- 2. However, superimposed PGE2 reduced J(Na) to 19.0 +/- 3.0. We conclude that PGE2 inhibits sodium transport predominantly by increasing intracellular calcium. This action is not mediated by a pertussis toxin-sensitive G protein. Finally, cAMP, through a cyclooxygenase-dependent mechanism, also inhibits CCD J(Na) and may contribute to the effects of PGE2 on J(Na) in the rabbit CCD.