کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8998168 | 1115605 | 2005 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Role of the α subunit in the modulation of GABAA receptors by anabolic androgenic steroids
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
Neural transmission mediated by circuits expressing α2 subunit-containing γ-aminobutyric acid type A (GABAA) receptors is critical for the expression of behaviors known to be altered by anabolic androgenic steroids (AAS). Here we show that micromolar concentrations of AAS, which reflect levels found in steroid abusers, induce positive modulation of currents from α2β3γ2L recombinant receptors elicited by pulses of GABA that mimic synaptic conditions in a manner that is mechanistically distinct from modulation induced at α1β3γ2L receptors. Specifically, at α2-containing receptors, the AAS, 17α-methyltestosterone (17α-MeT) enhanced peak current, slowed deactivation, diminished desensitization, and promoted entry of receptors into more distal states along the activation pathway. Analysis of GABAA receptor-mediated synaptic currents in primary cortical neurons followed by single cell real-time RT-PCR demonstrated that 17α-MeT enhancement of synaptic currents is proportional to the ratio of α2 to α1 subunit mRNA. Finally, we show that the modulation elicited by AAS is not comparable to that produced by micromolar concentrations of other positive allosteric modulators at α2-containing receptors. In sum, these data indicate that AAS elicit effects on GABAA receptor function that depend significantly on α subunit composition and that the mechanism of AAS modulation of GABAA receptors is distinct from that of other positive allosteric modulators.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 49, Issue 3, September 2005, Pages 300-316
Journal: Neuropharmacology - Volume 49, Issue 3, September 2005, Pages 300-316
نویسندگان
Paul Yang, Brian L. Jones, Leslie P. Henderson,