Cell-type Dependent Selectivity of CCK2R Signaling (Homo sapiens)

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PV+ basket cell Pyramidal cell12 CCK+ Basket Cell presynaptic terminalPertussis toxinGABA vesiclesendocannabinoidsCalcium storesGABA8-NH2-cADPRNEMCB1DAG lipaseDAGGi/0RyanodineCCKRYR1TRPC1GqPLCB1ADP-Ribose cyclaseCa 2+YM022CCK2RIP3 receptor2-APBYM022cyclic ADPRU-73122Flufenamic acidCCKCCK2RCa2+ storesendocannabinoidsCa 2+Ca 2+Ca 2+RYR2RYR3GABAGABAGABACa 2+Ca 2+Na +Na +Ca 2+Ca 2+RYR1RYR2RYR3


This pathway is based on Figure 7 of "Cell-Type Specific CCK2 Receptor Signaling Underlies the Cholecystokinin-Mediated Selective Excitation of Hippocampal Parvalbumin-Positive Fast-Spiking Basket Cells."(See Bibliography).The neuropeptide cholecystokinin (CCK) acts through its receptor CCK2R to achieve largely different functions in different types of cells. CCK, CCK2R, and CB1R have all been known to have substantial effects on anxiety and other mood disorders, and the PV+ interneurons have also been shown to be involved i na variety of cognitive functions. However, In PV+ basket cells and CCK+ basket cells, the CCK2 receptor uses different pathways to exert different effects on the two types of basket cells. For CCK+ basket cells, CCK2 receptors in neighboring pyramidal cells act through the Gq pathway to form endocannabinoids, which, through the cannabinoid receptor type 1 on the CCK+ basket cell, inhibit the release of the neurotransmitter GABA. In contrast, for PV+ basket cells, CCK2 receptors act through the pertussin-toxin sensitive Gi pathway to regulate the intracellular Ca2+ through ryanodine receptors. This pathway ultimately leads to activation of a non-selective cationic conductance to depolarize the PV+ basket cells.

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Ontology Terms



  1. Lee SY, Földy C, Szabadics J, Soltesz I; ''Cell-type-specific CCK2 receptor signaling underlies the cholecystokinin-mediated selective excitation of hippocampal parvalbumin-positive fast-spiking basket cells.''; J Neurosci, 2011 PubMed Europe PMC
  2. Lee SH, Soltesz I; ''Requirement for CB1 but not GABAB receptors in the cholecystokinin mediated inhibition of GABA release from cholecystokinin expressing basket cells.''; J Physiol, 2011 PubMed Europe PMC


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96380view06:51, 11 March 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
96379view06:50, 11 March 2018EgonwFixed a character encoding issue.
94188view14:09, 25 August 2017Mkutmonadded missing metabolite identifier
93125view07:50, 31 July 2017DeSlreverted change of cyclic ADPR (Pubchem SID was wrong database, had to be Pubchem CID)
93102view16:10, 28 July 2017DeSlChanged pubchem sub ID to chemspider ID cyclic ADPR
90184view18:35, 21 October 2016Khanspersupdated catalysis
90111view19:32, 13 October 2016Khanspersxref update and layout
89166view03:41, 23 August 2016AriuttaOntology Term : 'signaling pathway' added !
88785view20:01, 14 August 2016AAR&CoModified title
88784view20:01, 14 August 2016AAR&CoEdited Nodes
88782view19:59, 14 August 2016AAR&CoAdded Data Node
88780view19:57, 14 August 2016AAR&CoAdded Data Nodes
88775view19:44, 14 August 2016AAR&CoOntology Term : 'basket cell' added !
88774view19:43, 14 August 2016AAR&CoOntology Term : 'pyramidal neuron' added !
88764view19:07, 14 August 2016AAR&CoAdd Comments
88761view18:59, 14 August 2016AAR&CoModify Labels
88760view18:57, 14 August 2016AAR&CoModify Datanodes
88757view18:47, 14 August 2016AAR&CoOntology Term : 'pertussis' added !
88756view18:46, 14 August 2016AAR&CoModify Datanode
88753view18:41, 14 August 2016AAR&CoPeriodical save, work in progress
88746view18:24, 14 August 2016AAR&CoPeriodical save, work in progress
88743view18:18, 14 August 2016AAR&CoModify Datanode
88612view00:55, 12 August 2016AAR&CoUnconnected lines
88599view20:01, 11 August 2016Mkutmonfix unconnected lines
88555view01:53, 11 August 2016AAR&CoFix unconnected lines
88553view01:48, 11 August 2016AAR&CoAdd citation
88552view01:47, 11 August 2016AAR&CoModified description
86138view13:19, 1 July 2016AAR&CoModified description
86137view13:18, 1 July 2016AAR&CoNew pathway

External references


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NameTypeDatabase referenceComment
2-APBMetaboliteQ4596857 (Wikidata)
8-NH2-cADPRMetabolite3081323 (PubChem-compound) artifically added antagonist of cyclic ADPR
ADP-Ribose cyclaseGeneProductENSG00000004468 (Ensembl)
CB1GeneProductENSG00000118432 (Ensembl) Cannabinoid receptor 1
CCK2RGeneProductENSG00000110148 (Ensembl) receptor
CCKGeneProductENSG00000187094 (Ensembl)
Ca 2+MetaboliteCHEBI:29108 (ChEBI)
DAG lipaseGeneProductENSG00000134780 (Ensembl)
DAGMetaboliteCHEBI:18035 (ChEBI)
Flufenamic acidMetaboliteCHEBI:42638 (ChEBI)
GABA Metabolite116 (Chemspider)
  • gamma-Aminobutyric acid
  • inhibitory neurotransmitter in mammalian CNS
Gi/0GeneProductENSG00000127955 (Ensembl)
GqGeneProductENSG00000156052 (Ensembl)
IP3 receptorGeneProductENSG00000150995 (Ensembl)
NEMMetabolite4209 (Chemspider)
Na +MetaboliteCHEBI:29101 (ChEBI)
PLCB1GeneProductENSG00000182621 (Ensembl)
RYR1GeneProductENSG00000196218 (Ensembl)
RYR2GeneProductENSG00000198626 (Ensembl)
RYR3GeneProductENSG00000198838 (Ensembl)
RyanodineMetabolite16736002 (Chemspider) artificially added inhibitor of ryanodine receptor
TRPC1GeneProductENSG00000144935 (Ensembl)
  • likely forms complexes with TRPC4 and TRPC5
  • transient receptor potential ion channel
U-73122MetaboliteQ27089044 (Wikidata)
YM022Metabolite122130 (PubChem-compound)
cyclic ADPRMetabolite123847 (PubChem-compound)

Annotated Interactions

No annotated interactions

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