In acutely isolated rat primary sensory neurons, the effects of caffeine on GABA receptormediated current (I GABA) were investigated using a whole-cell patch clamp technique. We found that applications of GABA (10-1000 μM) induced inward currents in a concentration-dependent manner; the currents manifested obvious desensitization. Pretreatment with caffeine (0.01-100 μM) suppressed I GABA in a noncompetitive manner; caffeine shifted the concentration–response curve for GABA downwards compared to the control. Theophylline showed a similar and stronger inhibitory effect on I GABA. Isolated application of 1 μM diazepam enhanced I GABA, while pretreatment with 10 μM caffeine and 1 μM diazepam suppressed this current. Intracellular application of the protein kinase A inhibitor H-8 dramatically weakened the inhibitory effect of caffeine on I GABA. Because primary afferent depolarization is related to GABAA receptors, our results suggest that caffeine might antagonize presynaptic inhibitory effects of primary afferents, probably via inhibition of intracellular phosphodiesterase.
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Yang, J.Y., Yang, G., Ren, J. et al. Caffeine Suppresses GABA Receptor-Mediated Current in Rat Primary Sensory Neurons via Inhibition of Intracellular Phosphodiesterase. Neurophysiology 47, 108–114 (2015). https://doi.org/10.1007/s11062-015-9506-1
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DOI: https://doi.org/10.1007/s11062-015-9506-1