کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9018118 | 1128688 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of leukocyte function and interleukin-2 gene expression by 2-methylarachidonyl-(2â²-fluoroethyl)amide, a stable congener of the endogenous cannabinoid receptor ligand anandamide
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کلمات کلیدی
NF-κBEMSANF-ATDEAEPhorbol-12-myristate-13-acetateionomycinΔ9-THCCB2forskolinIL-2AP-1CB1pKaPMSFFskCREBRT-PCRTBSPBSCBNCREcAMP - cAMPPMA - LDC هاElectrophoretic mobility shift assay - آزمون تحرک تحرک الکتروفورزanandamide - آناندامیدdiethyl aminoethyl - اتیل اتیل دی اتیلArachidonic acid - اسید آراشیدونیکCSA - ایالات مؤتلفهٔ آمریکاInterleukin-2 - اینترلوکین-۲Tris-buffered saline - تریس بافر شورELISA - تست الیزاEnzyme-linked immunosorbent assay - تست الیزاdelta-9-tetrahydrocannabinol - دلتا 9-تتراهیدروکانیابینولBCs - روند BCsbovine calf serum - سرم گوساله گوسالهT cells - سلول های تیcyclosporin A - سیکلوسپورین ANuclear Factor of Activated T Cells - عامل هسته ای سلول های T فعال شدهcAMP response element - عنصر پاسخ cAMPphenyl-methylsulfonyl fluoride - فنیل متیل سولفونیل فلورایدPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریReverse transcriptase-polymerase chain reaction - واکنش زنجیره ای واکنش زنجیره ای واکنش زنجیره ایcAMP response element binding protein - پروتئین اتصال دهنده عنصر پاسخ cAMPactivator protein 1 - پروتئین فعال کننده 1protein kinase A - پروتئین کیناز ACannabinoid - کانابینوئیدcannabinol - کانابینول
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Arachidonylethanolamide (anandamide, AEA) has been identified as an endogenous ligand for cannabinoid receptors CB1 and CB2. Characterization of the direct cannabimimetic actions of anandamide has been hampered by its short duration of action and rapid degradation in in vivo and in vitro systems to arachidonic acid, a precursor in the biosynthesis of a broad range of biologically active molecules. In the present studies, we utilized 2-methylarachidonyl-(2â²-fluoroethyl)amide (F-Me-AEA), an analog of anandamide resistant to enzymatic degradation, to determine whether F-Me-AEA modulated T cell function similar to that of plant-derived cannabinoids. Indeed, F-Me-AEA at low micromolar concentrations exhibited a marked inhibition of phorbol ester plus calcium ionophore (PMA/Io)-induced IL-2 protein secretion and steady state mRNA expression. Likewise, a modest suppression of the mixed lymphocyte response was observed in the presence of F-Me-AEA indicating an alteration in T cell responsiveness to allogeneic MHC class II antigens. F-Me-AEA was also found to modestly inhibit forskolin-stimulated adenylate cyclase activity in thymocytes and splenocytes, a hallmark of cannabinoid receptor agonists. Further characterization of the influence of F-Me-AEA on the cAMP signaling cascade revealed an inhibition of CREB-1/ATF-1 phosphorylation and subsequently, an inhibition of CRE DNA binding activity. Characterization of nuclear binding proteins further revealed that NF-AT and, to a lesser extent, NF-κB DNA binding activities were also suppressed. These studies demonstrate that F-Me-AEA modulates T cell function in a similar manner to plant-derived and endogenous cannabinoids and therefore can be utilized as an amidase- and hydrolysis-resistant endogenous cannabinoid.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 205, Issue 2, 1 June 2005, Pages 107-115
Journal: Toxicology and Applied Pharmacology - Volume 205, Issue 2, 1 June 2005, Pages 107-115
نویسندگان
Barbara L.F. Kaplan, Yanli Ouyang, Amy Herring, Sung Su Yea, Raj Razdan, Norbert E. Kaminski,