Caffeine Suppresses GABA Receptor-Mediated Current in Rat Primary Sensory Neurons via Inhibition of Intracellular Phosphodiesterase
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.
KeywordsGABA receptor-mesiated current primary sensory (DRG) neurons whole-cell patch clamp caffeine phosphodiesterase
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