کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10595247 981861 2012 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues
چکیده انگلیسی
The kappa opioid receptor (KOPR) has been identified as a potential drug target to prevent or alter the course of mood, anxiety and addictive disorders or reduce response to stress. In a search for highly potent and selective KOPR partial agonists as pharmacological tools, we have modified 12-epi-salvinorin A, a compound which we have previously observed to be a KOPR partial agonist. Five analogues of 12-epi-salvinorin A were synthesized and their effects on G protein activation as well as β-arrestin2 recruitment were evaluated. Only 12-epi-salvinorin A (1) partially activated signaling through G proteins, yet acted as a full agonist in the β-arrestin 2 DiscoveRx assay. Other salvinorin analogues tested in these functional assays were full agonists in both assays of KOPR activation. By comparison, the non-selective opioid ligand nalbuphine, known to be a partial agonist for G-protein activation, was also a partial agonist for the β-arrestin mediated signaling pathway activated through KOPR.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 2, 15 January 2012, Pages 1023-1026
نویسندگان
, , , , , , , , ,