Involvement of Postsynaptic EP4 and Presynaptic EP3 Receptors in Actions of Prostaglandin E2 in Rat Supraoptic Neurones
Involvement of Postsynaptic EP4 and Presynaptic EP3 Receptors in Actions of Prostaglandin E2 in Rat Supraoptic Neurones
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突触后 EP4 和突触前 EP3 受体参与前列腺素 E2 在大鼠视上神经元中的作用
DOI：
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发表时间：
2002
影响因子：
3.2
通讯作者：
H. Yamashita
中科院分区：
文献类型：
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作者：
I. Shibuya;S. Setiadji;N. Ibrahim;N. Harayama;T. Maruyama;Y. Ueta;H. Yamashita
前列腺素E_2（PGE_2）可能通过双重突触后PG受体、FP受体和未鉴定的EP受体兴奋视上核（SON）神经元，突触前EP受体也可能参与这种兴奋。在本研究中，为了阐明PGE 2介导的SON神经元作用的受体机制，我们使用细胞外记录和全细胞膜片钳技术研究了四种新开发的EP激动剂对大鼠SON神经元的突触前和突触后作用，这些激动剂对四种EP受体（EP 1 −4）中的每一种都具有选择性。EP 4激动剂ONO-AE 1 - 329模拟PGE 2的兴奋作用，而EP 1激动剂ONO-DI-004、EP 2激动剂ONO-AE 1 - 257和EP 3激动剂ONO-AE-248几乎没有或没有作用。ONO-AE 1 - 329的作用不受EP 1/FP/TP拮抗剂ONO-NT-012的影响，后者可有效抑制FP激动剂氟前列醇和PGE 2引起的兴奋。当重复应用氟前列醇使对氟前列醇的反应脱敏时，ONO-AE 1 - 329引起显著兴奋。SON神经元的膜片钳分析显示，ONO‐ AE 1 ‐329在保持电位为−70 mV时诱导内向电流，电流的反转电位为−35.1 ± 2.3 mV。 另一方面，从SON切片制备物记录的自发抑制性突触后电流的频率被ONO-AE-248抑制，但不受其他三种EP激动剂的影响。这些结果表明，SON神经元具有突触后EP 4受体，而支配SON神经元的γ-氨基丁酸神经元在其终末具有突触前EP 3受体。这两种EP受体的激活可能参与了PGE 2对SON神经元的兴奋性调节。
We have reported that supraoptic nucleus (SON) neurones are excited by prostaglandin E2 (PGE2) presumably via dual postsynaptic PG receptors, FP receptors and unidentified EP receptors, and that presynaptic EP receptors may also be involved in the excitation. In the present study, to clarify the receptor mechanism of the PGE2‐mediated actions on SON neurones, we studied the pre‐ and postsynaptic effects of four newly developed EP agonists that are selective for each of the four EP receptors, EP1−4, on rat SON neurones using extracellular recording and whole‐cell patch‐clamp techniques. The EP4 agonist ONO‐AE1‐329 mimicked the excitatory effects of PGE2, whereas the EP1 agonist ONO‐DI‐004, the EP2 agonist ONO‐AE1‐257 and the EP3 agonist ONO‐AE‐248 had little or no effect. The effects of ONO‐AE1‐329 were unaffected by the EP1/FP/TP antagonist, ONO‐NT‐012, which potently suppressed the excitation caused by the FP agonist fluprostenol and PGE2. ONO‐AE1‐329 caused marked excitation when responses to fluprostenol were desensitized by repeated applications of fluprostenol. Patch‐clamp analysis in SON neurones showed that ONO‐AE1‐329 induced inward currents at a holding potential of −70 mV and the reversal potential of the currents was −35.1 ± 2.3 mV. On the other hand, the frequency of spontaneous inhibitory postsynaptic currents recorded from SON slice preparations was suppressed by ONO‐AE‐248, but unaffected by the other three EP agonists. These results suggest that SON neurones possess postsynaptic EP4 receptors and that γ‐aminobutyric acid neurones innervating SON neurones possess presynaptic EP3 receptors in their terminals. Activation of the two EP receptors may be involved in the excitatory regulation of SON neurones by PGE2.
脑前列腺素在控制清醒大鼠加压素分泌中的作用。
影响因子：
4.8
作者：
Brooks,DP;Share,L;Crofton,JT
通讯作者：
Crofton,JT