PMID:20392936

Citation	Deng, PY, Xiao, Z, Jha, A, Ramonet, D, Matsui, T, Leitges, M, Shin, HS, Porter, JE, Geiger, JD and Lei, S (2010) Cholecystokinin facilitates glutamate release by increasing the number of readily releasable vesicles and releasing probability. J. Neurosci. 30:5136-48
Abstract	Cholecystokinin (CCK), a neuropeptide originally discovered in the gastrointestinal tract, is abundantly distributed in the mammalian brains including the hippocampus. Whereas CCK has been shown to increase glutamate concentration in the perfusate of hippocampal slices and in purified rat hippocampal synaptosomes, the cellular and molecular mechanisms whereby CCK modulates glutamatergic function remain unexplored. Here, we examined the effects of CCK on glutamatergic transmission in the hippocampus using whole-cell recordings from hippocampal slices. Application of CCK increased AMPA receptor-mediated EPSCs at perforant path-dentate gyrus granule cell, CA3-CA3 and Schaffer collateral-CA1 synapses without effects at mossy fiber-CA3 synapses. CCK-induced increases in AMPA EPSCs were mediated by CCK-2 receptors and were not modulated developmentally and transcriptionally. CCK reduced the coefficient of variation and paired-pulse ratio of AMPA EPSCs suggesting that CCK facilitates presynaptic glutamate release. CCK increased the release probability and the number of readily releasable vesicles with no effects on the rate of recovery from vesicle depletion. CCK-mediated increases in glutamate release required the functions of phospholipase C, intracellular Ca(2+) release and protein kinase Cgamma. CCK released endogenously from hippocampal interneurons facilitated glutamatergic transmission. Our results provide a cellular and molecular mechanism to explain the roles of CCK in the brain.
Links	PubMed PMC3073615 Online version:10.1523/JNEUROSCI.5711-09.2010
Keywords	Animals; Calcium/metabolism; Cholecystokinin/metabolism; Excitatory Postsynaptic Potentials/physiology; Glutamic Acid/metabolism; Hippocampus/growth & development; Hippocampus/physiology; Intracellular Space/physiology; Neurons/physiology; Potassium Channels/metabolism; Presynaptic Terminals/physiology; Probability; Protein Kinase C/metabolism; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin B/metabolism; Receptors, AMPA/metabolism; Synapses/physiology; Synaptic Transmission/physiology; Synaptic Vesicles/physiology; Type C Phospholipases/metabolism; gamma-Aminobutyric Acid/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:CCKN	involved_in	GO:0014049: positive regulation of glutamate secretion	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
RAT:CCKN		GO:0014049: positive regulation of glutamate secretion	ECO:0000314:		P		Fig 5 shows that CCK increases glutamate release through inhibition of calcium channels.	complete CACAO 6370

References

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