Prostaglandins of the E series inhibit monoamine release via EP3 receptors: proof with the competitive EP3 receptor antagonist L-826,266
Prostaglandins of the E series inhibit monoamine release via EP3 receptors: proof with the competitive EP3 receptor antagonist L-826,266
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DOI：
10.1007/s00210-009-0478-9
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发表时间：
2010-01-01
影响因子：
3.6
通讯作者：
Schlicker, E.
中科院分区：
文献类型：
--
作者：
Guenther, J.;Schulte, K.;Schlicker, E.
前列腺素E-2 （PGE(2)）及其类似物磺胺酮抑制啮齿动物组织中去甲肾上腺素和血清素的释放。我们研究了相关受体是否被EP3拮抗剂L-826,266阻断，这些受体是否也出现在中枢胆碱能神经元和视网膜多巴胺能细胞上，PGE(2)是否由内源性大麻素病毒胺降解产生，以及EP3受体激活是否刺激S-35- gtp γ S结合。在与h -3-去甲肾上腺素（在豚鼠视网膜中标记多巴胺能细胞）、h -3- 5 -羟色胺或h -3-胆碱预孵卵的过度组织中，研究电诱发氚溢出的递质释放。在小鼠和豚鼠海马膜上研究了S-35- gtp γ S结合（G蛋白活化的量度）。L-826,266可拮抗磺胺酮对大鼠皮质去甲肾上腺素释放的影响，产生基于Schild图的pA(2)值为7.56。小鼠皮质和大鼠输精管（去甲肾上腺素释放）和大鼠皮质（血清素释放）的表观pA(2)值分别为7.55、7.87和7.67。PGE(2)不影响大鼠脑内乙酰胆碱释放和豚鼠视网膜内多巴胺释放。在7个小鼠组织中，去甲肾上腺素释放被磺胺酮抑制，而不受病毒胺的影响。S-35- gtp γ S结合未被磺胺酮改变，但被大麻素激动剂WIN 55,212-2刺激。E系列前列腺素通过EP3受体抑制单胺释放，其中L-826,266是一种竞争性拮抗剂。EP3受体抑制递质释放不存在于中枢胆碱能神经元和视网膜多巴胺能细胞。毒胺不能转化为PGE(2)。无法确定基于S-35- gtp γ S结合的EP3受体模型。
Prostaglandin E-2 (PGE(2)) and its analogue sulprostone inhibit noradrenaline and serotonin release in rodent tissues. We examined whether the receptor involved is blocked by the EP3 antagonist L-826,266, whether such receptors also occur on central cholinergic neurones and retinal dopaminergic cells, whether PGE(2) is produced by the degradation of the endocannabinoid virodhamine and whether EP3 receptor activation stimulates S-35-GTP gamma S binding. Transmitter release was studied as electrically evoked tritium overflow in superfused tissues preincubated with H-3-noradrenaline (which in the guinea pig retina labels dopaminergic cells), H-3-serotonin or H-3-choline. S-35-GTP gamma S binding, a measure of G protein activation, was studied in mouse and guinea pig hippocampal membranes. L-826,266 antagonised the effect of sulprostone on noradrenaline release in the rat cortex, yielding a Schild plot-based pA(2) value of 7.56. Apparent pA(2) values in mouse cortex and rat vas deferens (noradrenaline release) and rat cortex (serotonin release) were 7.55, 7.87 and 7.67, respectively. PGE(2) did not affect acetylcholine release in rat brain and dopamine release in guinea pig retina. In seven mice tissues, noradrenaline release was inhibited by sulprostone but not affected by virodhamine. S-35-GTP gamma S binding was not altered by sulprostone but stimulated by the cannabinoid agonist WIN 55,212-2. Prostaglandins of the E series inhibit monoamine release via EP3 receptors at which L-826,266 is a competitive antagonist. EP3 receptors that inhibit transmitter release are not present on central cholinergic neurones and retinal dopaminergic cells. Virodhamine is not converted to PGE(2). An EP3 receptor model based on S-35-GTP gamma S binding could not be identified.