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• W1498523518 endingPage "1910" @default.
• W1498523518 startingPage "1904" @default.
• W1498523518 abstract "Background and purpose: Although both natural and synthetic cannabinoid compounds have been shown to exert an antinociceptive effect on acute and persistent pain, the anatomical locus of the target of cannabinoid-induced analgesia has not been fully elucidated. Here, we investigated the effects of the cannabinoid agonist WIN 55,212-2 on GABA-activated currents (IGABA) in rat primary sensory neurones. Experimental approach: In the present study, experiments were performed on neurones freshly isolated from rat trigeminal ganglion (TG) by using whole-cell patch clamp and repatch techniques. Key results: GABA-evoked inward currents were potentiated by pretreatment with WIN 55,212-2 in a concentration-dependent manner (10−10–10−8 M). WIN 55,212-2 shifted the GABA concentration–response curve upwards, with an increase of 30.3 ± 3.7% in the maximal current response but with no significant change in the EC50 (agonist concentration producing a half-maximal response) value. WIN 55,212-2 potentiated the responses to GABA in a manner independent of holding potential and in the absence of any change in the reversal potential of the current. This potentiation of IGABA induced by WIN 55,212-2 was almost completely blocked by AM 251 (3 × 10−8 M), a CB1 receptor antagonist, and, using the repatch technique, was found to be abolished after intracellular dialysis with the protein kinase A (PKA) activator cAMP or the PKA inhibitor H89. Conclusions and implications: The potentiation by WIN 55,212-2 of IGABA in primary sensory neurones may help to elucidate the mechanism underlying the modulation of analgesia by cannabinoids in the spinal dorsal horn." @default.
• W1498523518 created "2016-06-24" @default.
• W1498523518 creator A5005002539 @default.
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• W1498523518 date "2009-11-16" @default.
• W1498523518 modified "2023-10-16" @default.
• W1498523518 title "Potentiation by WIN 55,212-2 of GABA-activated currents in rat trigeminal ganglion neurones" @default.
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• W1498523518 doi "https://doi.org/10.1111/j.1476-5381.2009.00482.x" @default.
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