کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5829951 | 1559012 | 2011 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Desensitization of adenosine A1 receptors in rat immature cortical neurons
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Desensitization of adenosine A1 receptors in rat immature cortical neurons Desensitization of adenosine A1 receptors in rat immature cortical neurons](/preview/png/5829951.png)
چکیده انگلیسی
Adenosine plays an important neuroprotective role in brain, usually mediated by the activation of adenosine A1 receptors. Prolonged activation of a G-protein-coupled receptor generally leads to the partial loss of the responsiveness of receptor-mediated transduction pathways (desensitization). Rat immature cortical neurons were treated with 100 nM (â)N6-phenylisopropyladenosine (R-PIA), a selective A1 receptor agonist, and the effect on adenosine A1 receptor/adenylyl cyclase pathway was studied. Incubation with R-PIA for 6, 12, 24 and 48 h elicited a time-dependent decrease in adenosine A1 receptors in plasma membranes (92, 58, 43 and 26% of control, respectively), which was associated with variations in microsomal fraction (21, 56, 124 and 233% of control, respectively), suggesting the internalization and down-regulation of adenosine A1 receptors. Moreover, real-time PCR assays showed a significant increase in mRNA levels coding adenosine A1 receptor after the longest treatment period (48 h). In addition, αGi1-2 protein levels detected in microsomes and mRNA levels coding αGi1 protein were increased after 48 h of treatment with R-PIA, suggesting the synthesis of new αGi1 proteins. Finally, adenylyl cyclase inhibition elicited by 2-Chloro-N6-cyclopentyladenosine (CPA), a selective adenosine A1 receptor agonist, was significantly reduced after 12, 24 and 48 h of treatment (37, 24 and 23%, respectively) as compared to controls (54%), suggesting the desensitization of adenosine A1 receptor/adenylyl cyclase pathway. These results suggest that adenosine A1 receptors desensitize slowly after prolonged receptor activation in immature cortical neurons, showing mechanisms of desensitization similar to those described not only in fetal but also in adult rat brain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 670, Issues 2â3, 30 November 2011, Pages 365-371
Journal: European Journal of Pharmacology - Volume 670, Issues 2â3, 30 November 2011, Pages 365-371
نویسندگان
MarÃa Ángeles Ruiz, David AgustÃn León, José Luis Albasanz, Mairena MartÃn,