کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2553363 1560755 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Agonist-specific down regulation of mu-opioid receptors: Different cellular pathways are activated by different opioid agonists
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Agonist-specific down regulation of mu-opioid receptors: Different cellular pathways are activated by different opioid agonists
چکیده انگلیسی

Opioid agonists are known to induce down regulation of opioid receptors through the classical pathway that involves phosphorylation, clathrin-dependent endocytosis and lysosomal/endosomal degradation of the internalized receptors. As expected, exposure of mu-opioid receptor (MOR)-transfected HEK-293 cells to either DAMGO (a specific mu-opioid agonist) or etorphine (a wide spectrum opioid agonist) resulted in down regulation of the receptors that was blocked by the kinase inhibitor staurosporine, by hypertonic sucrose and by the lysosomal and proteasomal inhibitors chloroquine and lactacystin. High concentration of etorphine, but not of DAMGO, induced an additional process of down regulation that was resistant to staurosporine, to hypertonic sucrose and to chloroquine–lactacystin. Etorphine, but not DAMGO, also induced down regulation of mu-opioid receptors in isolated membranes of HEK cells. This membrane-delimited down regulation was blocked by selective inhibitors of protease enzymes, suggesting the involvement of membranous serine- and amino-peptidases. This membranous down regulation of opioid receptors was dependent on the concentration of etorphine and was blocked by the opioid antagonist naloxone. Etorphine induced similar down regulation in membranes of HEK-293 cells transfected with delta-opioid receptors (DOR) as well in membranes of cells that endogenously express opioid receptors. This agonist-specific membrane-delimited regulatory process appears to be physiologically relevant and should be taken into account when studying long term effects of opioid drugs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 82, Issues 15–16, 9 April 2008, Pages 831–839
نویسندگان
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