Presynaptic kainate receptor facilitation of glutamate release involves protein kinase A in the rat hippocampus.
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 microm. 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.
Rodríguez-Moreno
Antonio
A
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Sihra
Talvinder S
TS
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004558:Electric Stimulation; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000262:Adenylyl Cyclases; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D007608:Kainic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic