Zusman R M, Keiser H R, Handler J S
J Clin Invest. 1977 Dec;60(6):1339-47. doi: 10.1172/JCI108893.
Prostaglandin E biosynthesis and its effect on water permeability were investigated in the toad urinary bladder. Arginine vasopressin (1 mU/ml) increased prostaglandin E (PGE) biosynthesis from 0.5+/-0.1 to 5.0+/-0.4 pmol/min per hemibladder (mean +/-SEM, n= 8, P less than 0.001). Maximal vasopressin-stimulated PGE biosynthesis, 6.4+/-0.2 pmol/min per hemibladder, occurred at vasopressin concentrations in excess of 3 mU/ml. Half-maximal stimulation of PGE biosynthesis occurred at a vasopressin concentration of approximately 0.7 mU/ml, whereas half-maximal stimulation of water flow occurred at a vasopressin concentration of approximately 5 mU/ml. Vasopressin-stimulated PGE biosynthesis did not depend on water flow along an osmotic gradient or upon sodium transport. Thin-layer chromatographic analysis of the lipids released from hemibladders labeled with tritium-arachidonic acid revealed that vasopressin stimulates the release of arachidonic acid from intracellular lipid stores without affecting the percentage of free arachidonic acid converted to PGE. Neither cyclic AMP nor theophylline stimulated PGE biosynthesis although they mimic arginine vasopressin (AVP) in stimulating water permeability. Biosynthesis of PGE was inhibited by mepacrine, a phospholipase inhibitor, and by agents that inhibit arachidonic acid oxygenase. The inhibition of PGE biosynthesis resulted in augmented vasopressin- and theophylline-stimulated water flow, but had no effect on cyclic AMP-stimulated water flow. We interpret these results to mean that endogenous PGE inhibits basal and vasopressin-stimulated adenylate cyclase activity. In contrast to the effects of AVP on permeability and transport, AVP stimulates PGE biosynthesis by a mechanism that does not depend on an increase in cellular cyclic AMP levels. The water permeability response of the toad urinary bladder to vasopressin is inhibited by PGE synthesized by the bladder in response to vasopressin.
在蟾蜍膀胱中研究了前列腺素E的生物合成及其对水通透性的影响。精氨酸血管加压素（1 mU/ml）使前列腺素E（PGE）的生物合成从每半膀胱0.5±0.1增加至5.0±0.4 pmol/分钟（平均值±标准误，n = 8，P＜0.001）。血管加压素刺激的PGE生物合成最大值为每半膀胱6.4±0.2 pmol/分钟，出现在血管加压素浓度超过3 mU/ml时。PGE生物合成的半最大刺激出现在血管加压素浓度约为0.7 mU/ml时，而水流量的半最大刺激出现在血管加压素浓度约为5 mU/ml时。血管加压素刺激的PGE生物合成不依赖于沿渗透梯度的水流或钠转运。对用氚标记的花生四烯酸标记的半膀胱释放的脂质进行薄层层析分析表明，血管加压素刺激花生四烯酸从细胞内脂质储存中释放，而不影响游离花生四烯酸转化为PGE的百分比。尽管环磷酸腺苷（cAMP）和茶碱在刺激水通透性方面模拟精氨酸血管加压素（AVP），但它们均不刺激PGE生物合成。PGE的生物合成受到磷脂酶抑制剂米帕林以及抑制花生四烯酸加氧酶的试剂的抑制。PGE生物合成的抑制导致血管加压素和茶碱刺激的水流量增加，但对cAMP刺激的水流量没有影响。我们将这些结果解释为内源性PGE抑制基础和血管加压素刺激的腺苷酸环化酶活性。与AVP对通透性和转运的影响相反，AVP通过不依赖于细胞内cAMP水平升高的机制刺激PGE生物合成。蟾蜍膀胱对血管加压素的水通透性反应受到膀胱响应血管加压素合成的PGE的抑制。
