Analysis of prostaglandig-mediated regulatory mechanisms in the neuronal and endocrine systems

前列腺素介导的神经元和内分泌系统调节机制分析

• 批准号: 12470013
• 负责人: SHIBUYA Izumi
• 金额: $ 9.41万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470013/
• 关键词: Prostaglandins; Neuroendocrine cells; Pituitary galnd; Adrenal medulla; Astrocytes; Patch clamp; Synaptic currents; Cytosolic Ca2+; Endocrine cells; DRG neurons; Prostaglandin

5) Astrocytes PGE_2, PGD_2, PGF_<2a>, but neither IPagonist U-46619 nor TP agonist carbacyclin, induced a rise in [Ca??], in cultured rat astrocytes. RT-PCR analysis of astrocytes revealed all known 8 PG receptor mRNAs. These multiple PG receptors may be involved in signal transduction via PGs in the CNS.To elicidate the precise cellular and molecular mechanisms involved in the prostaglandin (PG)-mediated regulation of neuronal and endocrine cells, we have examined membrane potentials, membrane currents, cytosolic Ca^<2+> concentration ([Ca^<2+>]) and mRNAs in several types of cells.1) Supraoptic nucleus (SON) neurons PGE_2 and PGF_<2a> caused an increase in the action potential discharge, cationic currents, somatodendritic release of oxytocin and vasopressin and in [Ca^<2+>]. These effects were mimicked by the selective EP_4 agonist ONO-AE1-329 and the FP agonist fluprostenol, while EP_1 agonist ONQ-DI-004, EP_2 agonist ONO-AE1-257 and EP_3 agonist ONO-AE-248 had little effect. PGE_2 … More but not PGF_<2a> reduced the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) without affecting the amplitude. This was mimicked by the EP_3 agonist but other three selective EPagonist had little effect. These results indicate that PG receptors are present both at the pre- and post-synaptic sites of SON neurons : postsynaptic EP_4 and FP receptors are coupled to non-selective cation channels, activation of which results in membrane depolarization and Ca^<2+> entry through voltage-gated Ca^<2+> channels ; and presynaptic EP_3 receptors in GABA neurons suppress GABA release, which results in disinhibition of SON neurons. These multiple excitatory mechanisms mediated by pre- and postsynaptic PG receptors may play important roles in the regulation of SON neurons by PGs.2) Adrenal chromaffin cells PGE_2 and ONO-DI-004 induced Ca?? release and Ca?? entry in cultured bovine adrenal chromaffin cells. RT-PCR analysis revealed that the adrenal medulla of rats express EP_1, EP_3, EP_4 receptor mRNAs, suggesting a role of EP1receptors in the chromaffin cells.3) Melanotrophs of the pituitary pars intermedia PGE_2, and ONO-AE-248 caused a reduction in [Ca^<2+>]. PGE_2 suppressed voltage-gated Ca^<2+> channel currents, but had little effect on inwardly rectifying K^+ currents. EP_3 receptor mRNA was detected in the pars intermedia tissue, suggesting EP_3 receptors are selectively coupled with voltage-gated Ca^<2+> channels.4) Dorsal root ganglion (DRG) neurons PGE_2, ONO-AE1-257 and ONO-AE1-328 induced a rise in [Ca^<2+>], in capsaicin-sensitive mouse DRG neurons, indicating EP_2 and EP_4 receptors are involved in nociception.6) Whole-animal experiments with mice Intracerebroventricular injection of any of the four selective EPagonists had little effect on drinking and other behaviors. Less

5)PGE_2、PGD_2、PGF_3均能引起星形胶质<2a>细胞[Ca ~（2+）] i升高，而IP激动剂U-46619和TP激动剂carbacyclin均不能引起[Ca ~（2+）] i升高。在培养的大鼠星形胶质细胞中。星形胶质细胞的RT-PCR分析显示了所有已知的8种PG受体mRNA。为了阐明前列腺素（PG）介导的神经细胞和内分泌细胞调节的确切细胞和分子机制，我们检测了膜电位、膜电流、膜电位和膜电位的变化，PGE_2和PGF_2引起视上核神经元<2a>动作电位放电、阳离子电流、催产素和加压素的释放以及胞浆Ca ^&lt;2+&gt;浓度的增加。EP_1激动剂ONQ-DI-004、EP_2激动剂ONO-AE 1 -257和EP_3激动剂ONO-AE-248对上述作用无明显影响。PGE_2 ...更多信息 而PGF_2则<2a>不影响自发抑制性突触后电流（IPSC）的幅度。EP_3激动剂可模拟此作用，而其它三种选择性EPagonists则无此作用。这些结果表明，PG受体存在于SON神经元的突触前和突触后部位：突触后EP_4和FP受体与非选择性阳离子通道偶联，激活该通道导致膜去极化和Ca^2+通过电压门控Ca^2+通道进入; GABA神经元突触前EP_3受体抑制GABA的释放，使SON神经元的抑制解除。突触前和突触后PG受体介导的多种兴奋机制可能在PG对SON神经元的调节中起重要作用。释放和钙？？进入培养的牛肾上腺嗜铬细胞。RT-PCR分析显示，大鼠肾上腺髓质表达EP_1、EP_3、EP_4受体mRNA，提示肾上腺髓质嗜铬细胞中存在EP_1受体。3）垂体中间部促黑素细胞PGE_2和ONO-AE-248可引起[Ca^2+]减少。PGE_2抑制电压门控性Ca^2+通道电流，但对内向整流性K^+通道电流影响不大。4）背根神经节（DRG）神经元PGE_2、ONO-AE 1 -257和ONO-AE 1 -328可诱导辣椒素敏感的小鼠DRG神经元[Ca^2+]升高，表明EP_2和EP_4受体参与伤害性感受。6）小鼠全动物实验：侧脑室注射四种选择性EPagonists对饮水和其他行为均无明显影响。少

项目成果

Shibuya I., Kabashima N., Setiadji V.S., lbrahim N., Ueta Y., Yamashita H.: "Pre- and postsynaptic modulation of t he neuronal act ivity of supraoptic neurones"Exp. physiol. 85. 145S-152S (2000)

Shibuya I.、Kabashima N.、Setiadji V.S.、lbrahim N.、Ueta Y.、Yamashita H.：“视上神经元的神经元活动的突触前和突触后调节”Exp。

Shibuya,I.: "The regulatory mechanism of the neuronal activity of hypothalamic supraoptic neurons."Experimental Neurobilology. 9. 51-59 (2001)

涩谷，I.：“下丘脑视上神经元的神经活动的调节机制。”实验神经生物学。

Shibuya, I.: "The regulatory mechanism of the neuronal activity of hypothalamic supraoptic neurons"Exp.Neurobiol.. 9. 51-59 (2000)

涩谷，I.：“下丘脑视上神经元的神经活动的调节机制”Exp.Neurobiol.. 9. 51-59 (2000)

Shiraishi S., Shibuya I., Uezono Y., Yokoo H., Toyohira Y., Yamamoto R., Yanagita T., Kobayashi H., Wada A.: "Heterogenous increases of cytoplasmic calcium : distinct effects on down-regulation of cell surface sodium channels and sodium channel subunit mR

Shiraishi S.、Shibuya I.、Uezono Y.、Yokoo H.、Toyohira Y.、Yamamoto R.、Yanagita T.、Kobayashi H.、Wada A.：“细胞质钙的异质性增加：对下调

Shibuya, I. et al.: "Pre-and postsynaptic modulation of the neuronal activity of supraoptic neurones"Exp.Physiol.. 85. 145S-152S (2000)

Shibuya, I. 等人：“视上神经元的神经元活动的突触前和突触后调节”Exp.Physiol.. 85. 145S-152S (2000)