Epoxygenase metabolites of arachidonic acid inhibit vasopressin response in toad bladder.
Epoxygenase metabolites of arachidonic acid inhibit vasopressin response in toad bladder.
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花生四烯酸的环氧酶代谢物抑制蟾蜍膀胱中的加压素反应。
DOI：
10.1152/ajprenal.1987.253.3.f464
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Levine,SD
中科院分区：
文献类型：
--
作者：
Schlondorff,D;Petty,E;Oates,JA;Jacoby,M;Levine,SD
除了环氧合酶和脂氧合酶途径外，肾脏还可以通过NADPH依赖性细胞色素P-450酶将花生四烯酸代谢为环氧二十碳三烯酸（EET）;此外，5，6-EET已被证明可以改变通过离体肾小管的电解质转运。本文研究了三种EET（5，6-，11，12-和14，15-EET）对蟾蜍膀胱渗透水流量的影响。所有三种EET都可逆地抑制加压素刺激的渗透水流，其中5，6-和11，12-EET最有效。这些作用似乎与洋地黄素无关。依地平抑制对毛喉素的水流反应，但不抑制（11，12-EET除外）对腺苷3 '，5'-环一磷酸（cAMP）或8-BrcAMP的反应，这与对cAMP生成的影响一致。对于11，12-EET，必须考虑在cAMP以外或独立于cAMP的位点处的额外抑制的问题。为了确定这些影响是否是由于雌二醇或其代谢产物，我们研究了其邻位二醇水解产物，二羟基二十碳三烯酸的影响。标记的5，6-EET的邻二醇的非酶转化迅速发生在缓冲液中，而11，12-EET仅在膀胱组织存在下孵育时以可饱和的方式水解。形成的二羟基二十碳三烯酸抑制水流的方式平行的EREX。5，6-EET和11，12-EET（10（-5）M）都可以阻止加压素刺激后对照组织中观察到的细胞内cAMP含量的增加。最后，11，12-和14，15-dihydroxyeicosatrienoic acid抑制加压素和毛喉素刺激的腺苷酸环化酶在相同的等级顺序，因为它们抑制水流。（250字处删节）
In addition to cyclooxygenase and lipoxygenase pathways, the kidney can also metabolize arachidonic acid by a NADPH-dependent cytochrome P-450 enzyme to epoxyeicosatrienoic acids (EETs); furthermore, 5,6-EET has been shown to alter electrolyte transport across isolated renal tubules. We examined the effects of three EETs (5,6-, 11, 12-, and 14,15-EET) on osmotic water flow across toad urinary bladder. All three EETs reversibly inhibited vasopressin-stimulated osmotic water flow with 5,6- and 11,12-EET being the most potent. The effects appeared to be independent of prostaglandins. EETs inhibited the water flow response to forskolin but not (with the exception of 11,12-EET) the response to adenosine 3',5'-cyclic monophosphate (cAMP) or 8-BrcAMP, consistent with an effect on cAMP generation. For 11,12-EET the question of an additional inhibition at a site beyond or independent of cAMP has to be considered. To determine whether these effects were due to the EETs or to products of their metabolism, we examined the effects of their vicinal diol hydrolysis products, the dihydroxyeicosatrienoic acids. Nonenzymatic conversion of labeled 5,6-EET to its vicinal diol occurred rapidly in the buffer, whereas 11,12-EET was hydrolyzed in a saturable manner only when incubated in the presence of bladder tissue. The dihydroxyeicosatrienoic acids formed inhibited water flow in a manner paralleling that of the EETs. Both 5,6-EET and 11,12-EET (10(-5) M) prevented the increase in intracellular cAMP content observed in control tissues after vasopressin stimulation. Finally, 11,12- and 14,15-dihydroxyeicosatrienoic acid inhibited vasopressin- and forskolin-stimulated adenylate cyclase in the same rank order as their inhibition of water flow.(ABSTRACT TRUNCATED AT 250 WORDS)