Prostaglandin E2 receptor EP3 subtype in the paraventricular hypothalamic nucleus mediates corticotropin-releasing factor-induced elevation of plasma noradrenaline levels in rats.
Prostaglandin E2 receptor EP3 subtype in the paraventricular hypothalamic nucleus mediates corticotropin-releasing factor-induced elevation of plasma noradrenaline levels in rats.
复制标题
下丘脑室旁核中的前列腺素 E2 受体 EP3 亚型介导促肾上腺皮质激素释放因子诱导的大鼠血浆去甲肾上腺素水平升高。
DOI：
10.1016/j.ejphar.2019.172693
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Okada S.
中科院分区：
文献类型：
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作者：
Yamaguchi N;Mimura K;Okada S.
促肾上腺皮质激素释放因子（CRF）在交感神经调节中发挥重要作用。集中施用 CRF 会升高血浆儿茶酚胺水平，导致 CRF 依赖性高血压和心动过速。我们之前报道过脑血栓素 A2 介导 CRF 诱导的血浆肾上腺素水平升高，而除血栓素 A2 之外的前列腺素类药物介导血浆去甲肾上腺素水平升高。然而，CRF 引起血浆去甲肾上腺素水平升高的机制仍不清楚。先前的研究表明，大脑前列腺素 (PG) E2（而非其他 PG）会引起交感神经激活。在这项研究中，我们研究了大脑 PGE2 及其受体在 CRF 诱导的大鼠血浆去甲肾上腺素水平升高中的作用。我们的结果表明，用 PGE2 受体 EP3 亚型拮抗剂（而非其他亚型）进行脑室内预处理，可以抑制 CRF 诱导的血浆去甲肾上腺素水平升高。我们还研究了室旁下丘脑核 (PVN) 中 PGE2 和 EP3 受体在 CRF 诱导的血浆去甲肾上腺素水平升高中的作用，PVN 是交感调节的主要综合中心。集中施用CRF可增加PVN微透析液中的PGE2水平，并且将EP3受体激动剂显微注射到PVN中可提高血浆去甲肾上腺素水平。双侧阻断 PVN 中的 EP3 受体可抑制脑室内给药和 CRF 的 PVN 微注射引起的血浆去甲肾上腺素水平升高。我们的结果表明，CRF 刺激 PGE2 释放到 PVN，激活 PVN 中的 EP3 受体，导致血浆去甲肾上腺素水平升高。
Corticotropin-releasing factor (CRF) plays an important role in sympathetic regulation. Centrally administered CRF elevates plasma catecholamine levels, resulting in CRF-dependent hypertension and tachycardia. We previously reported that brain thromboxane A2mediates CRF-induced elevation of plasma adrenaline levels, whereas prostanoids other than thromboxane A2mediate elevations in plasma noradrenaline levels. However, the mechanism by which CRF induces elevations in plasma noradrenaline levels remains unknown. Previous studies have revealed that brain prostaglandin (PG) E2, but not other PGs, causes sympathetic activation. In this study, we examined the roles of brain PGE2and its receptors in CRF-induced elevation of plasma noradrenaline levels in rats. Our results showed that intracerebroventricular pretreatment with an antagonist of the PGE2receptor EP3subtype, but not other subtypes, suppressed CRF-induced elevations in plasma noradrenaline levels. We also examined the role of PGE2and EP3receptors in the paraventricular hypothalamic nucleus (PVN), the major integrative center for sympathetic regulation, in CRF-induced elevation of plasma noradrenaline levels. Centrally administered CRF increased PGE2levels in PVN microdialysates, and microinjection of an EP3receptor agonist into the PVN elevated plasma noradrenaline levels. Bilateral blockade of EP3receptors in the PVN suppressed the elevation of plasma noradrenaline levels evoked by intracerebroventricular administration and PVN-microinjection of CRF. Our results suggest that CRF stimulates PGE2release into the PVN that activates EP3receptors in the PVN, resulting in the elevation of plasma noradrenaline levels.