Ibrahim N, Shibuya I, Kabashima N, Sutarmo S V, Ueta Y, Yamashita H
Department of Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
J Neuroendocrinol. 1999 Nov;11(11):879-86. doi: 10.1046/j.1365-2826.1999.00404.x.
Prostaglandin E2 (PGE2) has been implicated in the excitatory regulation of magnocellular neurones in the supraoptic nucleus (SON). We have recently reported that PGE2 excited SON neurones by directly activating postsynaptic PGE2 receptors (EP receptors) of a subclass other than EP1-3, but did not affect excitatory postsynaptic currents (EPSCs). In the present study, we examined presynaptic effects of PGE2 on rat SON neurones by measuring spontaneous inhibitory postsynaptic currents (IPSCs) by a slice patch-clamp technique. PGE2 inhibited spontaneous IPSCs in a dose-dependent and reversible manner. PGE2 selectively suppressed the frequency of IPSCs without affecting the amplitude of IPSCs in the presence of tetrodotoxin, a blocker of Na+ channels, indicating that the effects were presynaptic. The inhibitory effects of PGE2 on the frequency of IPSCs were mimicked by the EP1/EP3 agonists, 17PT-PGE2 and sulprostone, and the EP2/EP3 agonist, misoprostol, whereas the EP2 agonist, butaprost, or the FP agonist, fluprostenol, had little effect. The effects of PGE2 on IPSCs were unaffected by the selective EP1 antagonist, SC-51322. They were unaffected also by antagonists of GABAB and alpha2 adrenergic receptors, which are present at presynaptic terminals of GABA neurones in the SON and cause suppression of spontaneous IPSCs. The inhibitor of PG synthesis, indomethacin, had little effect on spontaneous IPSCs and on the inhibitory effects of PGE2 as well as of the GABAB agonist, baclofen, and noradrenaline. These results suggest that PGE2 inhibits release of GABA from the GABAergic terminals innervating SON neurones by activating presynaptic EP receptors, presumably of the EP3 subclass, and that such a presynaptic mechanism may play a role in the excitatory regulation of SON neurones by PGE2.
前列腺素E2（PGE2）与视上核（SON）中巨细胞神经元的兴奋性调节有关。我们最近报道，PGE2通过直接激活EP1 - 3以外的另一亚类突触后PGE2受体（EP受体）来兴奋SON神经元，但不影响兴奋性突触后电流（EPSCs）。在本研究中，我们通过切片膜片钳技术测量自发性抑制性突触后电流（IPSCs），研究了PGE2对大鼠SON神经元的突触前效应。PGE2以剂量依赖性和可逆的方式抑制自发性IPSCs。在存在Na + 通道阻滞剂河豚毒素的情况下，PGE2选择性地抑制IPSCs的频率而不影响其幅度，表明这些效应是突触前的。PGE2对IPSCs频率的抑制作用被EP1 / EP3激动剂17PT - PGE2和硫前列酮以及EP2 / EP3激动剂米索前列醇模拟，而EP2激动剂布他前列素或FP激动剂氟前列醇几乎没有影响。PGE2对IPSCs的作用不受选择性EP1拮抗剂SC - 51322的影响。它们也不受GABAB和α2肾上腺素能受体拮抗剂的影响，这些受体存在于SON中GABA能神经元的突触前终末并导致自发性IPSCs的抑制。PG合成抑制剂吲哚美辛对自发性IPSCs以及PGE2、GABAB激动剂巴氯芬和去甲肾上腺素的抑制作用几乎没有影响。这些结果表明，PGE2通过激活突触前EP受体（可能是EP3亚类）来抑制支配SON神经元的GABA能终末释放GABA，并且这种突触前机制可能在PGE2对SON神经元的兴奋性调节中起作用。
