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 -

基本信息

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

项目摘要

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

已知蛋氨酸-脑啡肽 (Met-Enk) 在受到烟碱乙酰胆碱 (Ach) 受体刺激时，会与肾上腺髓质嗜铬细胞中的儿茶酚胺 (CA) 共同释放。然而，肾上腺释放的 Met-Enk 的生理作用是。尚未得到澄清。在这项研究中，发现长时间暴露（6至24小时）的牛肾上腺髓质嗜铬细胞对尼古丁 (10μM) 的作用诱导了 Met-Enk 的持续释放，尽管 CA 的释放是短暂的。一种新鉴定的假定内源性促分泌素垂体腺苷酸环化酶激活多肽 (PACAP, 10nM) 引起了 Met-Enk 的持久分泌。长期Ach处理后嗜铬细胞中的CA和Met-Enk含量不但没有减少，甚至还增加。 PACAP 诱导的 CA 释放需要细胞外 CaD12+D1，但不受电压操作的 CaD12+D1 通道阻滞剂、A-激酶抑制剂或 C-激酶抑制剂的抑制。各种阿片类激动剂对 CA r 释放的影响尽管 Met-Enk 是这些亚型的 μ-和 δ-激动剂，但也对嗜铬细胞进行了研究。相反，强啡肽 A(1-13) 等 κ 激动剂可显着减少 Ach 诱导的 CA 释放，而 κ 特异性或非特异性阿片拮抗剂也不会拮抗这种抑制作用，强啡肽 A(1-13) 也不会抑制 Ach 诱导的细胞内 Ca。嗜铬细胞中的 D12+D1 浓度升高，两种强啡肽类似物 A(1-8) 和 A(2-13) 均被发现具有这种作用。对 κ 受体的活性较低或没有，显示出与 A(1-13) 相似的作用。相反，高 K-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的 CA 释放。不通过 Met-Enk 进行自动调节，但可能受到另一个涉及强啡肽的系统的调节，因此阿片类药物的 κ 亚型与 μ 或 δ Ach 亚型发挥着不同的作用。 CA 的释放，而 PACAP 应该负责 CA 的连续长期释放，而 PACAP 应该负责 Met-Enk 的连续长期释放和增强。Met-Ek 的作用需要进一步研究。。较少的