RGD Reference Report - Activation of corticotropin-releasing factor 2 receptor inhibits Purkinje neuron P-type calcium currents via G(o)alpha-dependent PKC epsilon pathway. - Rat Genome Database

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Activation of corticotropin-releasing factor 2 receptor inhibits Purkinje neuron P-type calcium currents via G(o)alpha-dependent PKC epsilon pathway.

Authors: Tao, J  Zhang, Y  Huang, H  Jiang, X 
Citation: Tao J, etal., Cell Signal. 2009 Sep;21(9):1436-43. Epub 2009 May 9.
RGD ID: 5130951
Pubmed: PMID:19439178   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cellsig.2009.05.002   (Journal Full-text)

Corticotropin-releasing factor (CRF) receptors have been demonstrated to be widely expressed in the central nervous system and in many peripheral tissues of mammalians. However, it is still unknown whether CRF receptors will function in cerebellar Purkinje neurons. In the present study, we investigated the expression profile of CRF receptors in rat cerebellum and identified a novel functional role of CRFR2 in modulating Purkinje neuron P-type Ca(2+) currents (P-currents). We found that CRFR2alpha mRNA, but not CRFR1 and CRFR2beta, was endogenously expressed in rat cerebellum. Activation of CRFR2 by UCN2 inhibited P-currents in a concentration-dependent manner (IC(50) approximately 0.07 microM). This inhibitory effect was abolished by astressin2B, a CRFR2 antagonist, and was blocked by GDP-beta-S, pertussis toxin, or a selective antibody raised against the G(o)alpha. Inhibition of phospholipase C (PLC) blocked the inhibitory action of UCN2. The application of diacylglycerol (DAG) antagonist, 1-hexadecyl-2-acetyl-sn-glycerol, as well as inhibition of either protein kinase C or its epsilon isoform (PKCepsilon) abolished the UCN2 effect while 1-oleoyl-2-acetyl-sn-glycerol (EI-150), a membrane-permeable DAG analogue, occluded UCN2-mediated inhibition. In addition, UCN2 significantly increases spontaneous firing frequency of Purkinje neurons in cerebellar slices. In summary, activation of CRFR2 inhibits P-currents in Purkinje neurons via G(o)alpha-dependent PLC/PKCepsilon pathway, which might contribute to its physiological functions in the cerebellum.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of calcium ion import  IMP 5130951 RGD 
protein kinase C-activating G protein-coupled receptor signaling pathway  IMP 5130951 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Crhr2  (corticotropin releasing hormone receptor 2)

Objects referenced in this article
Gene CRHR2 corticotropin releasing hormone receptor 2 Homo sapiens
Gene Crhr2 corticotropin releasing hormone receptor 2 Mus musculus

Additional Information