کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4330072 | 1614241 | 2008 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Labetalol facilitates GABAergic transmission to rat periaqueductal gray neurons via antagonizing β1-adrenergic receptors - A possible mechanism underlying labetalol-induced analgesia
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Labetalol, a combined α1, β1, and β2 adrenoceptor-blocking drug, has been shown to have analgesic properties in vivo. To determine the underlying mechanisms, we examined its effects on GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous firings of rat ventrolateral periaqueductal gray (PAG) neurons, either mechanically dissociated, or in acute brain slices. These PAG neurons mediate opioid-mediated analgesia and pain transmission and are under tonic control of GABAergic interneurons. An increase in GABAergic transmission to these neurons yields an inhibitory hyperpolarized state and may interrupt pain signal transmission. Using patch clamp techniques, we found that labetalol reversibly increases the frequency of sIPSCs without changing their mean amplitude. This indicates that labetalol enhances GABAergic synaptic transmission by a presynaptic mechanism. Metoprolol, a specific β1-adrenoceptor antagonist, also reversibly enhanced sIPSC frequency. In the presence of metoprolol, labetalol-induced increase in sIPSC frequency was significantly attenuated or even abolished. These results suggest that labetalol shares the same pathway as metoprolol in enhancing GABAergic transmission via an inhibition of presynaptic β1-adrenoceptors. We further showed that labetalol reversibly reduced the firing rate of PAG neurons. This reduction was significantly attenuated in the presence of bicuculline, a selective antagonist of GABAA receptors. These data indicate that labetalol-induced inhibition of PAG cell firing is attributable to its potentiation of GABAergic transmission. Based on these data, we postulate that labetalol-induced analgesia is at least in part ascribed to its antagonistic effects on presynaptic β1-adrenoceptors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1198, 10 March 2008, Pages 34-43
Journal: Brain Research - Volume 1198, 10 March 2008, Pages 34-43
نویسندگان
Cheng Xiao, Chunyi Zhou, Glen Atlas, Ellise Delphin, Jiang Hong Ye,