Study of the secretion of atrial natriuretic peptide (ANP) induced by morphine.

吗啡诱导心房钠尿肽（ANP）分泌的研究。

基本信息

批准号：
63570717
负责人：
KUDO Tsuyoshi
金额：
$ 0.96万
依托单位：
Hirasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570717/
关键词：
ANP Morphine Enkepharin Dynorphin Catecholamine Rat Atrium cell Naloxane フェンタニールオピオイド受容体 c-GMP ACTH CompB

项目摘要

1)In vivo experiment: Effects of morphine, feritanyl, dynorphin, enkepharin, beta-endorphin and naloxone on immunoreactive atrial natriuretic peptide (ir-ANP) levels in the plasma were investigated in conscious and unstrained male wistar rats. High dose of morphine and fentanyl induced a significant increase in plasma levels of ir-ANP concentration, but none of other opioide peptides induced such a increase. Significant increases in plasma cyclic GMP levels as well as ir-ANP were observed in morphine and fentanyl groups. Cyclic GMP was strongly implicated as a second messenger for ir-ANP. The increase in plasma cyclic GMP was well correlated with the increase of plasma ir-ANP levels. These significant increases were completely blocked by naloxone which was a strong, antagonist to opiate receptor of mu type. These results suggest that a high dose of morphine would increase plasma ir-ANP via morphine receptor. Furthermore, the marked increases of plasma catecholamine (NE and E) were observed as well as ir-ANP and cGMP by morphine and fentanyl. This observation would indicate a possible involvement of endogeneous catecholamine with opiate receptor in the reguration of ir-ANP secretion.2)In vitro experiment: The rat atrium cells were obtained by the enzyme dissociation of atrium. The cells were incubated with opioide peptides and catecholamines under the condition of 95% O and 5% CO with 38 C for 4 h. The concentration of ir-ANP in medium of culture tubes were increased by dynorphin and catecholamine but not another peptide. The combination of dynorphin and catecholamine markedly increased ir-ANP secretion from atrium cells, Especially. the combination with dopamine induced 10 fold increase than that of NE and E. These increase in ir-ANP were not blocked by naloxone.These results from the experiments of in vivo and in vitro suggest that endogeneous catecholamines involved in the secretion of ANP induced by large dose of morphine.

1)体内实验：在清醒和不紧张的雄性Wistar大鼠中研究吗啡、铁坦尼、强啡肽、脑啡肽、β-内啡肽和纳洛酮对血浆中免疫反应性心房钠尿肽(ir-ANP)水平的影响。高剂量的吗啡和芬太尼诱导血浆 ir-ANP 浓度显着增加，但其他阿片肽均未诱导这种增加。在吗啡和芬太尼组中观察到血浆环 GMP 水平以及 ir-ANP 显着增加。环 GMP 被强烈认为是 ir-ANP 的第二信使。血浆环鸟苷酸的增加与血浆ir-ANP水平的增加密切相关。这些显着的增加被纳洛酮完全阻断，纳洛酮是mu型阿片受体的强拮抗剂。这些结果表明，高剂量的吗啡会通过吗啡受体增加血浆 ir-ANP。此外，吗啡和芬太尼还观察到血浆儿茶酚胺（NE 和 E）以及 ir-ANP 和 cGMP 显着增加。这一观察结果表明内源性儿茶酚胺与阿片受体可能参与ir-ANP分泌的调节。2)体外实验：通过心房酶解获得大鼠心房细胞。将细胞与阿片肽和儿茶酚胺在95％O和5％CO的条件下38℃孵育4小时。培养管培养基中ir-ANP的浓度被强啡肽和儿茶酚胺增加，但另一种肽则没有增加。强啡肽和儿茶酚胺的组合显着增加了心房细胞的 ir-ANP 分泌，尤其是。与多巴胺联合诱导的ANP增加是NE和E的10倍。ir-ANP的增加不受纳洛酮的阻断。体内和体外实验的这些结果表明，内源性儿茶酚胺参与了NE和E诱导的ANP的分泌。大剂量吗啡。