The Function of Opioid Peptides Derived from Adrenal Medulla - Relationship to Stress and Immune System -

肾上腺髓质阿片肽的功能 - 与压力和免疫系统的关系 -

• 批准号: 09671895
• 负责人: IMAI Yasuo
• 金额: $ 1.92万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671895/
• 关键词: ardenal medulla; opioid; receptor; chromaffin cell; methionin-enkephalin; catecholamine; PACAP; dynorphin; オピオイド; ストレス; アセチルコリン; ニコチン

Methionine -enkephakin(Met-Enk) has been known to be co-released with catecholamine(CA) from adrenal medullary chromaffin cells when stimulated via nicotinic acetylcholine(Ach) receptor. The physiological role of released Met-Enk from adrenal gland, however, has not been clarified yet.In this study, it was found that a long time exposure (6 to 24 hrs) of bovine adrenal medullary chromaffin cells to nicotine (10μM) induced a continuous release of Met-Enk, although CA release was transient. A newly-identified putative endogenous secretagogue, pituitary adenylate cyclase-activating polypeptide (PACAP, 10nM) evoked a long-lasting secretion of CA and Met-Enk. The CA content in chromaffin cells was not decreased after long-term Ach treatment, but even increased by PACAP. PACAP-induced CA release required extracellular CaィイD12+ィエD1 but was not inhibited by voltage-operated CaィイD12+ィエD1 channel blockers, A-kinase inhibitors, nor C-kinase inhibitor.The effects of various opioid agonists on CA r … More elease in chromaffin cells were also investigated. Though Met-Enk is a μ-, and δ-agonists of these subtypes did not affect CA release. In contrast, κ-agonists like Dynorphin A(1-13) significantly reduced Ach-induced CA release. This inhibition was not antagonized by neither κ-specific nor non-specific opioid antagonists. Dynorphin A(1-13) also inhibited Ach-induced intracellular CaィイD12+ィエD1 concentration rise in chromaffin cells. Both dynorphin analogs, A(1-8) and A(2-13), which have been found to have less or no activity on κ-receptor, showed similar effects to A(1-13). In contrast, high KィイD1+ィエD1- nor PACAP-induced CA release was not affected by opioids. These results suggests that CA release from adrenal chromaffin cells is not autoregulated with Met-Enk, but may be regulated by another system involving dynorphin, thus κ subtype of opioids are plays different roles from μ or δ subtypes. Ach makes transient release of CA, while PACAP are supposed to be responsible for successive long-lasting release of CA, while PACAP are supposed to be responsible for successive long-lasting release and enhancement of Met-Enk production. The role of Met-Enk needs farther investigation. Less

已知当通过烟碱乙酰胆碱（Ach）受体刺激时，甲硫氨酸-脑啡肽（Met-Enk）与儿茶酚胺（CA）从肾上腺髓质嗜铬细胞共同释放。本研究发现，牛肾上腺嗜铬细胞长期暴露于尼古丁（10μM）（6 ~ 24小时）后，尽管CA释放是短暂的，但仍能引起Met-Enk的持续释放。一种新发现的内源性促分泌素-垂体腺苷酸环化酶激活多肽（PACAP，10 nM）可诱导CA和Met-Enk的长期分泌。长期Ach处理后，嗜铬细胞CA含量不降低，PACAP处理后，CA含量反而升高。PACAP诱导的CA释放需要细胞外Ca ~（2+）D_（12+）D_（12+）D_（11）通道，但不被电压操纵的Ca ~（2+）D_（12+）D_（12+）通道阻断剂、A激酶抑制剂或C激酶抑制剂所抑制。 ...更多信息 同时观察了嗜铬细胞的释放。虽然Met-Enk是这些亚型的μ-和δ-激动剂，但不影响CA释放。相比之下，κ-激动剂如强啡肽A（1-13）显著减少Ach诱导的CA释放。这种抑制作用不被κ特异性或非特异性阿片拮抗剂拮抗。强啡肽A（1-13）也抑制乙酰胆碱诱导的嗜铬细胞内Ca ~（2+）D_1浓度升高。强啡肽类似物A（1-8）和A（2-13）对κ受体的作用与A（1-13）相似，但对κ受体的作用较弱或无作用。相比之下，高K β D1+ β D1- nor PACAP诱导的CA释放不受阿片类药物的影响。这些结果表明，肾上腺嗜铬细胞CA的释放不受Met-Enk的自动调节，而可能受另一个强啡肽系统的调节，因此κ亚型阿片样物质与μ或δ亚型阿片样物质在肾上腺嗜铬细胞CA的释放中起不同的作用。Ach使CA短暂释放，PACAP使CA持续释放，PACAP使Met-Enk持续释放并增强Met-Enk的产生。Met-Enk的作用有待进一步研究。少