RGD Reference Report - Pharmacology and functional properties of NTS2 neurotensin receptors in cerebellar granule cells. - Rat Genome Database

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Pharmacology and functional properties of NTS2 neurotensin receptors in cerebellar granule cells.

Authors: Sarret, P  Gendron, L  Kilian, P  Nguyen, HM  Gallo-Payet, N  Payet, MD  Beaudet, A 
Citation: Sarret P, etal., J Biol Chem 2002 Sep 27;277(39):36233-43.
RGD ID: 727385
Pubmed: PMID:12084713   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M202586200   (Journal Full-text)

The binding and signaling properties of neuronal NTS2 neurotensin (NT) receptors were examined in cultured rat cerebellar granule cells. As shown by reverse transcription-PCR, receptor autoradiography, and confocal microscopic localization of fluorescent NT, these cells selectively express the NTS2 receptor subtype. Accordingly, a single apparent class of (125)I-NT-binding sites, with an affinity of 3.1 nm, was detected in cerebellar granule cell cultures. This binding was competed for with high affinity (IC(50) = 5.7 nm) by the NTS2 ligand levocabastine and with low affinity (IC(50) = 203 nm) by the NTS1 antagonist SR48692. Hypertonic acid stripping of surface-bound ligand and hyperosmolar sucrose treatment revealed that 64% of specifically bound (125)I-NT was internalized at equilibrium via a clathrin-dependent pathway. In cells loaded with the Ca(2+)-sensitive fluorescent dye Fluo4, SR48692, but neither NT nor levocabastine, triggered a marked increase in cytosolic [Ca(2+)](i). By contrast, both NT and levocabastine, but not SR48692, induced a sustained (>60 min) activation of the mitogen-activated protein kinases, p42/p44, indicating functional coupling of NTS2 receptors. Complementary experiments carried out on synaptosomes from adult rat cerebellum demonstrated the presence of presynaptic NTS2 receptors. However, in contrast to perikaryal NTS2 sites, these presynaptic receptors did not internalize in response to NT stimulation. Taken together, the present results demonstrate that NTS2 receptors are present both presynaptically and postsynaptically in central neurons and that NT and levocabastine act as agonists on these receptors.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ntsr1Ratnegative regulation of release of sequestered calcium ion into cytosol  IMP  RGD 
Ntsr2Ratpositive regulation of MAPK cascade  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ntsr1  (neurotensin receptor 1)
Ntsr2  (neurotensin receptor 2)


Additional Information