کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9416759 | 1292982 | 2005 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Anesthetic effects of progesterone are undiminished in progesterone receptor knockout mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Progesterone has sedative and anesthetic effects but the underlying molecular mechanisms remain unclear. The two possible mechanisms by which progesterone affects the function of the brain include binding to intracellular progesterone receptors (PR) and metabolism to GABAA receptor-modulating neurosteroids. In this study, PR knockout (PRKO) mice were used as model to study the role of PRs in the anesthetic activity of progesterone. The progesterone-induced anesthetic activity was undiminished in female PRKO mice (ED50, 172 mg/kg) as compared to their wild-type littermates (ED50, 167 mg/kg). The progesterone-induced anesthetic activity was highly correlated with increased plasma allopregnanolone levels. Pretreatment of PRKO mice with the 5α-reductase inhibitor finasteride significantly reduced the progesterone-induced anesthetic activity. Allopregnanolone also evoked dose-dependent anesthetic activity in PRKO mice, which was similar to those of wild-type mice. Thus, the anesthetic activity of progesterone is not mediated by its interaction with PRs. The neurosteroid allopregnanolone partially mediates the anesthetic activity of progesterone by potentiation of GABAA receptor function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1033, Issue 1, 1 February 2005, Pages 96-101
Journal: Brain Research - Volume 1033, Issue 1, 1 February 2005, Pages 96-101
نویسندگان
Doodipala S. Reddy, Leigh Ann Apanites,