Document Detail

Characterization of the effect of SR48692 on inositol monophosphate, cyclic GMP and cyclic AMP responses linked to neurotensin receptor activation in neuronal and non-neuronal cells.
MedLine Citation:
PMID:  8528577     Owner:  NLM     Status:  MEDLINE    
1. Neurotensin stimulated inositol monophosphate (IP1) formation in both human colonic carcinoma HT29 cells and in mouse neuroblastoma N1E115 cells with EC50 values of 3.5 +/- 0.5 nM (n = 4) and 0.46 +/- 0.02 nM (n = 3), respectively. Neurotensin also stimulated cyclic GMP production with an EC50 of 0.47 +/- 1.2 nM and inhibited cyclic AMP accumulation induced by forskolin (0.5 microM) with an IC50 of 1.33 +/- 1.5 nM (n = 3) on the N1E115 cell line. 2. The competitive antagonism by the non-peptide neurotensin receptor antagonist, SR48692 of neurotensin-induced IP1 formation revealed pA2 values of 8.7 +/- 0.2 (n = 3) for HT29 and 10.1 +/- 0.2 (n = 3) for N1E115 cells. SR48692 also antagonized the cyclic GMP and cyclic AMP responses induced by neurotensin in the N1E115 cell line with pA2 values of 10.7 +/- 0.7 (n = 3) and 9.8 +/- 0.3 (n = 3), respectively. 3. In CHO cells transfected with the rat neurotensin receptor, neurotensin stimulated IP1 and cyclic AMP formation with EC50 values of 3.0 +/- 0.5 nM (n = 3) and 72.2 +/- 20.7 nM (n = 3), respectively. Both effects were antagonized by SR48692, giving pA2 values of 8.4 +/- 0.1 (n = 3) for IP1 and 7.2 +/- 0.4 (n = 3) for cyclic AMP responses. 4. Radioligand binding experiments, performed with [125I]-neurotensin (0.2 nM), yielded IC50 values of 15.3 nM (n = 2) and 20.4 nM (n = 2) for SR48692 versus neurotensin receptor binding sites labelled in HT29 and N1E115 cells, respectively. 5 In conclusion, SR48692 appears to be a potent, species-independent antagonist of the signal transduction events triggered by neurotensin receptor activation in both neuronal and non-neuronal cell systems.
F Oury-Donat; O Thurneyssen; N Gonalons; P Forgez; D Gully; G Le Fur; P Soubrie
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  116     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1995 Sep 
Date Detail:
Created Date:  1996-02-01     Completed Date:  1996-02-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1899-905     Citation Subset:  IM    
Sanofi Recherche, Montpellier, France.
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MeSH Terms
Carcinoma / drug therapy*
Cell Line
Colon / drug effects
Cyclic AMP / pharmacology*
Cyclic GMP / pharmacology*
Dose-Response Relationship, Drug
Inositol Phosphates / metabolism
Neuroblastoma / drug therapy
Neurotensin / pharmacology*
Pyrazoles / pharmacology*
Quinolines / pharmacology*
Receptors, Neurotensin / antagonists & inhibitors*
Reg. No./Substance:
0/Inositol Phosphates; 0/Pyrazoles; 0/Quinolines; 0/Receptors, Neurotensin; 146362-70-1/SR 48692; 39379-15-2/Neurotensin; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP

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