The European journal of neuroscience
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Comparative Study
Taurine potentiates presynaptic NMDA receptors in hippocampal Schaffer collateral axons.
We have previously shown that activation of presynaptic N-methyl-d-aspartate (NMDA) receptors (NMDAR) enhances the amplitude of the presynaptic fibre volley (FV) evoked in Schaffer collateral axons of rat hippocampal slices, by a mechanism independent of extracellular Ca(2+). Here we compared the pharmacological characteristics of presynaptic NMDARs affecting axon excitability (activated by 10-300 microM NMDA for 10 min), with those mediating field excitatory postsynaptic potentials (NMDA-fEPSP). We found that NMDA-induced potentiation was completely inhibited by NVP-AAM077, an antagonist of NR2A-containing NMDAR, but not by ifenprodil, an NR2B-selective antagonist. ⋯ Surprisingly, the enhancing effect of taurine on NMDA-induced FV potentiation was blocked when it was co-applied with glycine. Furthermore, the glutamate released synaptically with a train of stimuli also increased FV amplitude by a mechanism dependent on NMDARs; this was potentiated by taurine but not by co-application of taurine and glycine. These results reveal that presynaptic NMDARs have unique properties that mediate the facilitation of axon excitability.
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Protein kinase C epsilon (PKCepsilon) is an important intracellular signaling molecule in primary afferent nociceptors, implicated in acute and chronic inflammatory as well as neuropathic pain. In behavioral experiments inflammatory mediators produce PKCepsilon-dependent hyperalgesia only in male rats. The mechanism underlying this sexual dimorphism is unknown. ⋯ In contrast, injection of estrogen preceding the activation of Epac completely abrogates the Epac-induced mechanical hyperalgesia. Our results suggest that gender differences in nociception do not reflect the use of generally different mechanisms. Instead, a common set of signaling pathways can be modulated by hormones.
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Previous data indicate that the release of somatodendritic dopamine in substantia nigra influences motor activity and coordination, but the relative importance of somatodendritic dopamine release vs. terminal striatal dopamine release remains to be determined. We utilized simultaneous measurement of dopamine neurotransmission by microdialysis and motor performance assessment by rotarod test to investigate the effects of local dopamine depletion in rats. The vesicular monoamine transporter inhibitor tetrabenazine (100 microm) was administered locally in substantia nigra as well as in striatum. ⋯ Striatal tetrabenazine administration decreased striatal dopamine dialysate concentrations to 5% of baseline and doubled the somatodendritic dopamine response to motor activity, but it was not associated with changes in motor performance or dopamine content in striatal tissue. Simultaneous treatment of substantia nigra and striatum reduced motor performance to 58 +/- 5% of the pretreatment value. The results of this study indicate that partial depletion of nigral dopamine stores can significantly impair motor functions, and that increased nigral dopamine release can counteract minor impairments of striatal dopamine transmission.