کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5813847 | 1556616 | 2015 | 32 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Investigation of the role of βarrestin2 in kappa opioid receptor modulation in a mouse model of pruritus
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کلمات کلیدی
MORGRK35′-guanidinonaltrindolenorBNIGPCRCPADMSO - DMSOG protein coupled receptor - G پروتئین همراه با پروتئینU50,488H - U50، 488[35S]GTPγS - [35S] GTPγSpruritus - خارشDimethyl sulfoxide - دیمتیل سولفواکسیدBiased ligand - لیگاند متناوبconditioned place aversion - ناامیدی محل سکونتNor-binaltorphimine - نور باینلورفیمیمwild type - نوع وحشیKOR - وقتیChloroquine phosphate - کلروکین فسفاتkappa opioid receptor - گیرنده اپوئیدی کاپاپMu opioid receptor - گیرنده اپیدمی م
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
The kappa opioid receptor (KOR) is involved in mediating pruritus; agonists targeting this receptor have been used to treat chronic intractable itch. Conversely, antagonists induce an itch response at the site of injection. As a G protein-coupled receptor (GPCR), the KOR has potential for signaling via G proteins and βarrestins, however, it is not clear which of these pathways are involved in the KOR modulation of itch. In this study asked whether the actions of KOR in pruritus involve βarrestins by using βarrestin2 knockout (βarr2-KO) mice as well as a recently described biased KOR agonist that biases receptor signaling toward G protein pathways over βarrestin2 recruitment. We find that the KOR antagonists nor-binaltorphimine (NorBNI) and 5â²-guanidinonaltrindole (5â²GNTI) induce acute pruritus in C57BL/6J mice, with reduced effects in KOR-KO mice. βArr2-KO mice display less of a response to KOR antagonist-induced itch compared to wild types, however no genotype differences are observed from chloroquine phosphate (CP)-induced itch, suggesting that the antagonists may utilize a KOR-βarrestin2 dependent mechanism. The KOR agonist U50,488H was equally effective in both WT and βarr2-KO mice in suppressing CP-induced itch. Furthermore, the G protein biased agonist, Isoquinolinone 2.1 was as effective as U50,488H in suppressing the itch response induced by KOR antagonist NorBNI or CP in C57BL/6J mice. Together these data suggest that the antipruritic effects of KOR agonists may not require βarrestins.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 99, December 2015, Pages 600-609
Journal: Neuropharmacology - Volume 99, December 2015, Pages 600-609
نویسندگان
Jenny Morgenweck, Kevin J. Frankowski, Thomas E. Prisinzano, Jeffrey Aubé, Laura M. Bohn,