Source:http://linkedlifedata.com/resource/pubmed/id/10456290
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
1999-9-21
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| pubmed:abstractText |
Corticotropin-releasing factor (CRF) is a hypothalamic 41-amino acid peptide which stimulates corticotropin (ACTH) release from the anterior pituitary and is also involved in the body response to stress. CRF1 receptors represent a potential target for novel antidepressant/anxiolytic drugs. The aim of the present study was to search for a human cell line expressing native, functional CRF1 receptors as a starting material for screening purposes. We identified CRF1 receptors functionally coupled to cAMP formation in human neuroblastoma SH-SY5Y cells. CRF induced concentration-dependent increases in cAMP accumulation in SH-SY5Y cells (maximal increase 6.9 +/- 0.9 fold over basal values, n = 14). This effect was mimicked by related peptides with similar potencies: (mean pEC50 value) human/rat CRF (8.63), rat urocortin (9.32), sauvagine (8.97), urotensin I (8.93), ovine CRF (8.81). The efficacies of these agonists were nearly the same, with the exception of ovine CRF which was slightly less efficacious (75% the Emax of CRF). The responses to CRF were competitively antagonised by the following peptide fragments (mean pKB value): alpha-helical-CRF (9-41) (7.54), [D-Phe12,Nle21,38,C alpha MeLeu37]CRF (12-41) (8.36) and [D-Tyr12]astressin (9.49) and by the selective, non-peptidic CRF1 receptor antagonists, CP-154,526 (7.76) and antalarmin (9.19). Estimation of receptor density by [125I]Tyr0-ovine CRF saturation binding yielded a modest number of binding sites (Bmax 12 fmol/mg protein, KD 0.2 nM). Analysis of mRNA by reverse transcription-polymerase chain reaction clearly revealed the presence of mRNA for CRF1 receptors in SH-SY5Y cells. A slight signal for CRF2 receptor mRNA was also observed. We conclude that neuroblastoma SH-SY5Y cells are endowed with native CRF1 receptors positively coupled to cAMP formation. They therefore constitute a useful functional model for the search of CRF1 selective compounds with potential anxiolytic/antidepressant activity.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:issn |
0767-3981
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
13
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
484-9
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| pubmed:dateRevised |
2004-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10456290-Animals,
pubmed-meshheading:10456290-Cyclic AMP,
pubmed-meshheading:10456290-Humans,
pubmed-meshheading:10456290-Neuroblastoma,
pubmed-meshheading:10456290-RNA, Messenger,
pubmed-meshheading:10456290-Radioligand Assay,
pubmed-meshheading:10456290-Rats,
pubmed-meshheading:10456290-Receptors, Corticotropin-Releasing Hormone,
pubmed-meshheading:10456290-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10456290-Sheep,
pubmed-meshheading:10456290-Tumor Cells, Cultured
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| pubmed:year |
1999
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| pubmed:articleTitle |
Functional, endogenously expressed corticotropin-releasing factor receptor type 1 (CRF1) and CRF1 receptor mRNA expression in human neuroblastoma SH-SY5Y cells.
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| pubmed:affiliation |
Nervous System Research, Mental Health Unit, Novartis Pharma AG, CH-4002 Basel, Switzerland.
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| pubmed:publicationType |
Journal Article
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