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• W2108553691 abstract "Norepinephrine has potent antiepileptic properties, the pharmacology of which is unclear. Under conditions in which GABAergic inhibition is blocked, norepinephrine reduces hippocampal cornu ammonis 3 (CA3) epileptiform activity through α₂ adrenergic receptor (AR) activation on pyramidal cells. In this study, we investigated which α₂AR subtype(s) mediates this effect. First, α₂AR genomic expression patterns of 25 rat CA3 pyramidal cells were determined using real-time single-cell reverse transcription-polymerase chain reaction, demonstrating that 12 cells expressed α_2AAR transcript; 3 of the 12 cells additionally expressed mRNA for α_2CAR subtype and no cells possessing α_2BAR mRNA. Hippocampal CA3 epileptiform activity was then examined using field potential recordings in brain slices. The selective αAR agonist 6-fluoronorepinephrine caused a reduction of CA3 epileptiform activity, as measured by decreased frequency of spontaneous epileptiform bursts. In the presence of βAR blockade, concentration-response curves for AR agonists suggest that an α₂AR mediates this response, as the rank order of potency was 5-bromo-<i>N</i>-(4,5-dihydro-1<i>H</i>-imidazol-2-yl)-6-quinoxalinamine (UK-14304) ≥ epinephrine >6-fluoronorepinephrine > norepinephrine ⋙ phenylephrine. Finally, equilibrium dissociation constants (<i>K</i>_b) of selective αAR antagonists were functionally determined to confirm the specific α₂AR subtype inhibiting CA3 epileptiform activity. Apparent <i>K</i>_b values calculated for atipamezole (1.7 nM), MK-912 (4.8 nM), BRL-44408 (15 nM), yohimbine (63 nM), ARC-239 (540 nM), prazosin (4900 nM), and terazosin (5000 nM) correlated best with affinities previously determined for the α_2AAR subtype (<i>r</i> = 0.99, slope = 1.0). These results suggest that, under conditions of impaired GABAergic inhibition, activation of α_2AARs is primarily responsible for the antiepileptic actions of norepinephrine in the rat hippocampal CA3 region." @default.
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• W2108553691 date "2007-03-06" @default.
• W2108553691 modified "2023-09-27" @default.
• W2108553691 title "α_2A Adrenergic Receptor Activation Inhibits Epileptiform Activity in the Rat Hippocampal CA3 Region" @default.
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• W2108553691 doi "https://doi.org/10.1124/mol.106.031773" @default.
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