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• W2122536684 abstract "Labetalol, a combined alpha1, beta1, and beta2 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 beta1-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 beta1-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 beta1-adrenoceptors." @default.
• W2122536684 created "2016-06-24" @default.
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• W2122536684 date "2008-03-01" @default.
• W2122536684 modified "2023-09-26" @default.
• W2122536684 title "Labetalol facilitates GABAergic transmission to rat periaqueductal gray neurons via antagonizing β1-adrenergic receptors — A possible mechanism underlying labetalol-induced analgesia" @default.
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• W2122536684 doi "https://doi.org/10.1016/j.brainres.2008.01.023" @default.
• W2122536684 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2276360" @default.
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