کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8550263 | 1562029 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Early changes in M2 muscarinic acetylcholine receptors (mAChRs) induced by sarin intoxication may be linked to long lasting neurological effects
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کلمات کلیدی
CIEM2 muscarinic acetylcholine receptorclathrin-independent endocytosisGPCRmAChRCDEG-protein-coupled receptors - G-پروتئین گیرندهACh - آهOrganophosphate - ارگانوفسفاتAcetylcholine - استیل کولینClathrin-dependent endocytosis - اندوسیتوز وابسته به کلاتینOrganophosphate compounds - ترکیبات ارگانوفسفرهSarin - سرینBrain damage - ضربه مغزیCHE - کهCholinesterase - کولین استرازmuscarinic acetylcholine receptor - گیرنده استیل کولین muscarinic
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
The effect of sarin on the binding parameters (KD & Bmax) of M2 muscarinic acetylcholine receptor (mAChR) was studied 24 h and 1 week post exposure. Male & female Sprague-Daweley rats were poisoned with 1XLD50 sarin (80 μg/kg, im) followed by treatment of trimedoxime bromide and atropine (7.5:5 mg/kg, im) 1 min later. Brains were removed and analyzed for M2 mAChR binding, using [3H]AFDX384, an M2 selective antagonist. A significant increase in KD of M2 mAChR was found in the cortex 24 h post poisoning, displaying elevation from 4.65 ± 1.16 to 8.45 ± 1.06 nM and 5.24 ± 0.93 to 9.29 ± 1.56 nM in male and female rats, respectively. A rise in KD was also noted 1 week following exposure from 5.04 ± 1.20 to 11.75 ± 2.78 and from 5.37 ± 1.02 to 11.66 ± 1.73 nM, presenting an added increase of 51 and 40% (compared to 24 h) in males and females, respectively. Analysis of M2 receptor density (Bmax) revealed a significant reduction of 68% in males and insignificant reduction of 22% in females, 24 h after sarin exposure which was followed by 37% recovery in males and 100% recovery in females, 1 week later. These results indicate that sarin induces a long-term decreased affinity in M2 mAChR (elevated KDs) and a transient effect on the number of this receptor subtype (Bmax). We hypothesize that the reduced affinity of the M2 receptors (negative auto-regulatory receptors) may cause long-term brain deficits by impairing the normal regulation release of ACh into the synaptic cleft.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: NeuroToxicology - Volume 65, March 2018, Pages 248-254
Journal: NeuroToxicology - Volume 65, March 2018, Pages 248-254
نویسندگان
Zipora Pittel, Shlomi Lazar, Rellie Gez, Shira Chapman,