Effects of Loperamide and Other Opioid-Related Substances on the Transcriptional Regulation of the Rat Pro-Opiomelanocortin Gene in AtT20 Cells
Effects of Loperamide and Other Opioid-Related Substances on the Transcriptional Regulation of the Rat Pro-Opiomelanocortin Gene in AtT20 Cells
复制标题
洛哌丁胺和其他阿片类药物相关物质对 AtT20 细胞中大鼠阿片黑皮质素原基因转录调控的影响
作者：
A. Nomura;Y. Iwasaki;Y. Aoki;E. Yamamori;N. Mutsuga;Masanori Yoshida;M. Asai;Y. Oiso;H. Saito
Although opioid peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis, their role in pro-opiomelanocortin (POMC) gene expression at the pituitary level is not known. We therefore examined the effects of opioid receptor agonists, including recently discovered endogenous opioid peptides, on POMC gene expression using the AtT20PL cell line, a subclone of AtT20 in which the rat POMC 5′-promoter-luciferase fusion gene was stably incorporated. The endogenous µ-opioid receptor agonists endomorphin 1 and 2 had no effect on either basal or corticotropin-stimulating-hormone-induced POMC expression. This was also the case with the δ-agonist BUBUC, the ĸ-agonist U50488H and the orphan receptor agonist orphanin FQ. In contrast, the synthetic µ-agonist loperamide significantly inhibited basal and yet enhanced cAMP-induced POMC expression. The inhibitory effect of loperamide was mimicked by the calmodulin antagonist W7 and antagonized by the calcium channel blocker nifedipine, whereas neither the inhibitory nor the enhancing effect of loperamide was influenced by the opioid antagonist naloxone. These results suggest that the synthetic µ-agonist loperamide has a modulatory effect on the 5′-promoter activity of the POMC gene. This effect does not seem to be mediated through the classical µ-opioid receptor but rather in part through a calcium/calmodulin-related mechanism.
大鼠下丘脑和垂体中的下丘脑-垂体-肾上腺活性和阿片黑皮质素原 mRNA 水平在有或没有限水应激的情况下受到急性间歇吗啡的差异调节。
DOI：
10.1677/joe.0.1630261
发表时间：
1999
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Zhou,Y;Spangler,R;Maggos,CE;Wang,XM;Han,JS;Ho,A;Kreek,MJ
通讯作者：
Kreek,MJ
影响因子：
2.5
作者：
Martin-Schild, S;Gerall, AA;Zadina, JE
通讯作者：
Zadina, JE