کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8537210 | 1561007 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
5-HT1B receptor agonist CGS12066 presynaptically inhibits glutamate release in rat hippocampus
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
pKaPBSPTXGPCRCGP37157TTXmEPSCs4-APHBMVGLUT1H89GDHHEPES buffer mediumVDCCFura-2-AM - 2-فورا-AM4-aminopyridine - 4-آمینوپیریدین6-Cyano-7-nitroquinoxaline-2,3-dione - 6-Cyano-7-nitroquinoxaline-2،3-dioneBSA - BSAD(−)-2-amino-5-phosphonopentanoic acid - D (-) - 2-amino-5-phosphonopentanoic acidd-AP5 - D-AP5DiSC3(5) - DiSC3 (5)[Ca2+]i - [Ca2 +] iω-conotoxin MVIIC - ω-کنوتوکسین MVIICadenylate cyclase - آدنیلات سیکلاسbovine serum albumin - آلبومین سرم گاوglutamate release - انتشار گلوتاماتtetrodotoxin - تترو دوتوکسین miniature excitatory postsynaptic currents - جریانهای پسینپتیک هیجان انگیز مینیاتوریCNS - دستگاه عصبی مرکزیpertussis toxin - سموم سورافنیCNQX - سیانکیوایکسcentral nervous system - سیستم عصبی مرکزیhippocampal synaptosomes - سیناپتوزوم هیپوکامپAntidepressant - ضدافسردگیFura-2-acetoxymethyl ester - فورا 2-اتوکسی متیل استرPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریprotein kinase A - پروتئین کیناز AVoltage-dependent Ca2+ channel - کانال Ca2 + وابسته به ولتاژglutamate dehydrogenase - گلوتامات دهیدروژناز5-HT1B receptors - گیرنده های 5-HT1BG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
CGS12066, a 5-hydroxytryptamine 1B (5-HT1B) receptor agonist, has been reported to exhibit antidepressant activity. Considering that glutamatergic dysfunction is implicated in depression, the effect of CGS12066 on glutamate release in rat hippocampal nerve terminals and possible underlying mechanism were investigated. We observed that CGS12066 inhibited 4-aminopyridine (4-AP)-evoked glutamate release, and that a 5-HT1B receptor antagonist blocked this inhibition. Western blot analysis and immunocytochemistry confirmed the presence of presynaptic 5-HT1B receptor proteins. CGS12066-mediated inhibition of 4-AP-evoked glutamate release was completely abolished in the synaptosomes pretreated with inhibitors of Gi/Go-protein, adenylate cyclase (AC), and protein kinase A (PKA), namely pertussis toxin, MDL12330A, and H89, respectively. CGS12066 reduced the elevation of 4-AP-evoked intrasynaptosomal Ca2+ and cyclic AMP (cAMP) levels, but did not affect the synaptosomal membrane potential. Furthermore, in the presence of Ï-conotoxin MVIIC, a N- and P/Q-type channel blocker, CGS12066-mediated inhibition of 4-AP-evoked glutamate release was markedly reduced; however, the intracellular Ca2+-release inhibitors dantrolene and CGP37157 did not affect the CGS12066 effect. Furthermore, CGS12066 reduced glutamatergic miniature excitatory postsynaptic current (mEPSC) frequency but did not affect mEPSC amplitude or glutamate-activated currents in hippocampal slices. Our data are the first to suggest that CGS12066 reduces AC/cAMP/PKA activation, through the activation of Gi/Go protein-coupled 5-HT1B receptors present on hippocampal nerve terminals, subsequently reducing Ca2+ entry through voltage-dependent Ca2+ channels and reducing 4-AP-evoked glutamate release. This investigation into the role of 5-HT1B receptors in glutamate release provides crucial information regarding the potential therapeutic role of 5-HT1B receptors for treating depression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Progress in Neuro-Psychopharmacology and Biological Psychiatry - Volume 86, 30 August 2018, Pages 122-130
Journal: Progress in Neuro-Psychopharmacology and Biological Psychiatry - Volume 86, 30 August 2018, Pages 122-130
نویسندگان
Cheng Wei Lu, Tzu Yu Lin, Shu Kuei Huang, Su Jane Wang,