Forskolin increases osmotic water permeability of rabbit cortical collecting tubule.
Forskolin increases osmotic water permeability of rabbit cortical collecting tubule.
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Forskolin 增加兔皮质集合管的渗透水渗透性。
DOI：
10.1007/bf01868442
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Anderson,RJ
中科院分区：
文献类型：
--
作者：
Dillingham,MA;Kim,JK;Horster,MF;Anderson,RJ
毛喉素是一种独特的二萜，可直接激活腺苷酸环化酶的催化亚基。因此，我们研究了50 μmforskohn对体外灌流的家兔皮质集合小管渗透水通透性的影响。毛喉素增加了所有肾小管的净体积流量（Jv，从0.30增加到1.22 nl/mm/min，P<0.02）。毛喉素的水渗透作用在幅度和时间过程方面与最大剂量（250 μU/ml）精氨酸加压素产生的水渗透作用相似。当同时给予最大浓度的毛喉素和精氨酸加压素时，未观察到对JvandLp的累加效应。化合物d（CH 2）5 Tyr（Et）VAVP，其非竞争性抑制加压素受体，显着降低收集管水渗透反应精氨酸加压素。与此相反，在d（CH 2）5 Tyr（Et）VAVP的存在下，对毛喉素的水渗透反应得以维持。而1.0 μ m鸟嘌呤5′-（β，γ-亚氨基）三磷酸（GppNHp）和钙调素抑制剂N-（6-amenohexyl）-5-chloro-1-naphthalensulfonamide（W-7）可抑制毛喉素的水渗透反应。这些结果表明，毛喉素在哺乳动物肾单位中发挥水渗透作用，其发生不依赖于加压素受体。鸟苷酸调节蛋白可能调节毛喉素的渗透水通透性效应。最后，钙调素是需要充分表达的影响，毛喉素，以增加渗透水通量。
Forskolin is a unique diterpene that may directly activate the catalytic subunit of adenylate cyclase. We therefore examined the effect of 50 μmforskohn on osmotic water permeability in rabbit cortical collecting tubules perfusedin vitro. Forskolin increased net volume flux (Jv, from 0.30 to 1.22 nl/mm/min,P<0.02) in all tubules. The hydro-osmotic effect of forskolin was similar with respect to magnitude and time course to that produced by a maximal dose (250 μU/ml) of arginine vasopressin. An additive effect onJvandLpwas not observed when maximal concentrations of forskolin and arginine vasopressin were given simultaneously. The compound d(CH2)5Tyr(Et) VAVP, which noncompetitively inhibits the vasopressin receptor, significantly reduced collecting tubular hydro-osmotic response to arginine vasopressin. In contrast, the hydro-osmotic response to forskolin was maintained in the presence of d(CH2)5Tyr(Et)VAVP. However, the hydro-osmotic response to forskolin could be inhibited by 1.0 μmguanine 5′-(β,γ-imido) triphosphate (GppNHp) and by the calmodulin inhibitor N-(6-amenohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). These results demonstrate that forskolin exerts an hydro-osmotic effect in the mammalian nephron which occurs independent of the vasopressin receptor. Guanine nucleotide regulatory proteins may modulate the osmotic water permeability effect of forskolin. Finally, calmodulin is required for full expression of the effect of forskolin to increase osmotic water flux.