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This Article Full Text Full Text (PDF) All Versions of this Article: 557/3/733    most recent jphysiol.2004.065029v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rodríguez-Moreno, A. Articles by Sihra, T. S. Search for Related Content PubMed PubMed Citation Articles by Rodríguez-Moreno, A. Articles by Sihra, T. S.

Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK

We have explored the mechanisms involved in the facilitation of glutamate release mediated by the activation of kainate receptors in the rat hippocampus using isolated nerve terminal (synaptosome) and slice preparations. In hippocampal nerve terminals, kainate (KA) produced an increase of glutamate release at concentrations of agonist ranging from 10 to 1000 µM. In hippocampal slices, KA at low nanomolar concentrations (20–50 nM) also produced an increase of evoked excitatory postsynaptic currents (eEPSCs) at mossy fibre–CA3 synapses. In both, synaptosomes and slices, the effect of KA was antagonized by CNQX, and persisted after pretreatment with a cocktail of antagonists for other receptors whose activation could potentially have produced facilitation of release. These data indicate that the facilitation of glutamate release observed is mediated by the activation of presynaptic glutamate receptors of the kainate type. Mechanistically, the observed effects of KA appear to be the same in synaptosomal and slice preparations. Thus, the effect of KA on glutamate release and mossy fibre–CA3 synaptic transmission was occluded by the stimulation of adenylyl cyclase by forskolin and suppressed by the inhibition of protein kinase A by H-89 or Rp-Br-cAMP. We conclude that kainate receptors present at presynaptic terminals in the rat hippocampus mediate the facilitation of glutamate release through a mechanism involving the activation of an adenylyl cyclase–second messenger cAMP–protein kinase A signalling cascade.

(Received 20 March 2004; accepted after revision 16 April 2004; first published online 23 April 2004)
Corresponding author T. S. Sihra: Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: t.sihra{at}ucl.ac.uk

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