کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5813509 | 1556607 | 2016 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacological characterization of EN-9, a novel chimeric peptide of endomorphin-2 and neuropeptide FF that produces potent antinociceptive activity and limited tolerance
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
Morphine (PubChem CID: 5288826)ED50NTIi.c.v.GPCRNPFFintracerebroventricularlyi.p.β-FNAEC50Forskolin (PubChem CID: 47936)CPAIBMXi.v.Naloxone (PubChem CID: 5464092)s.c.RF9EM-23-isobutyl-1-methylxanthine - 3-ایزوبوتیل-1-متیلکسانتینAUC - AUCcAMP - cAMPG-protein-coupled receptor - G-پروتئین گیرندهOpioid - opioidCyclic adenosine monophosphate - آدنوزین مونوفسفات CyclicNaltrindole - آن را بشکنیدendomorphin-2 - آندومورفین 2Beta-funaltrexamine - بتا فوپالترکسامینanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceintraperitoneal - داخل صفاقیIntravenous - داخل وریدی%MPE - درصد MPECNS - دستگاه عصبی مرکزیsubcutaneous - زیر جلدیcentral nervous system - سیستم عصبی مرکزیAntinociception - ضد انعقادarea under the curve - منطقه تحت منحنیconditioned place aversion - ناامیدی محل سکونتNor-BNI - نور BNINor-binaltorphimine - نور باینلورفیمیمneuropeptide FF - نوروپپتید FFChimeric peptide - پپتید Chimeric
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Mounting evidences indicate the functional interactions between neuropeptide FF (NPFF) and opioids, including the endogenous opioids. In the present work, EN-9, a chimeric peptide containing the functional domains of the endogenous opioid endomorphin-2 (EM-2) and NPFF, was synthesized and pharmacologically characterized. In vitro cAMP assay demonstrated that EN-9 was a multifunctional agonist of κ-opioid, NPFF1 and NPFF2 receptors. In the mouse tail-flick test, intracerebroventricularly (i.c.v.) administration of EN-9 produced significant antinociception with an ED50 value of 13.44 nmol, which lasted longer than that of EM-2. In addition, EN-9 induced potent antinociception after both intravenous (i.v.) and subcutaneous (s.c.) injection. Furthermore, the experiments using the antagonists of opioid and NPFF receptors indicated that the central antinociception of EN-9 was mainly mediated by κ-opioid receptor, independently on NPFF receptors. Notably, the central antinociception of EN-9 was not reduced over a period of 6 days repeated i.c.v. injection. Repeated i.c.v. administration of EN-9 with the NPFF1 and NPFF2 receptors antagonist RF9 resulted in a progressive loss of analgesic potency, consistent with the development of tolerance. Moreover, central administration of EN-9 induced the place conditioning aversion only at a high dose of 60 nmol, but not at low doses. At supraspinal level, only high dose of EN-9 (60 nmol, i.c.v.) inhibited gastrointestinal transit via NPFF receptors. Similarly, systemic administration of EN-9 also inhibited gastrointestinal transit at high doses (10 and 30 mg/kg, i.v.). Taken together, the multifunctional agonist of κ-opioid and NPFF receptors EN-9 produced a potent, non-tolerance forming antinociception with limited side effects.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 108, September 2016, Pages 364-372
Journal: Neuropharmacology - Volume 108, September 2016, Pages 364-372
نویسندگان
Zi-long Wang, Ning Li, Pei Wang, Hong-hai Tang, Zheng-lan Han, Jing-jing Song, Xu-hui Li, Hong-ping Yu, Ting Zhang, Run Zhang, Biao Xu, Meng-na Zhang, Quan Fang, Rui Wang,