Skip to Main content Skip to Navigation
Journal articles

Characterization of binding sites of a new neurotensin receptor antagonist, [3H]SR 142948A, in the rat brain.

Abstract : The present study describes the characterization of the binding properties and autoradiographic distribution of a new nonpeptide antagonist of neurotensin receptors, [3H]SR 142948A (2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3-dimethylaminopropyl)-N-methyl carbamoyl)-2-isopropylphenyl)-1H-pyrazole-3-carbonyl]-amino]-ad amantane-2-carboxylic acid, hydrochloride), in the rat brain. The binding of [3H]SR 142948A in brain membrane homogenates was specific, time-dependent, reversible and saturable. [3H]SR 142948A bound to an apparently homogeneous population of sites, with a Kd of 3.5 nM and a Bmax value of 508 fmol/mg of protein, which was 80% higher than that observed in saturation experiments with [3H]neurotensin. [3H]SR 142948A binding was inhibited by SR 142948A, the related nonpeptide receptor antagonist, SR 48692 (2-[[1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole -3-carbonyl]amino]-adamantane-2-carboxylic acid) and neurotensin. Saturation and competition studies in the presence or absence of the histamine H1 receptor antagonist, levocabastine, revealed that [3H]SR 142948A bound with similar affinities to both the levocabastine-insensitive neurotensin NT1 receptors (20% of the total binding population) and the recently cloned levocabastine-sensitive neurotensin NT2 receptors (80% of the receptors) (Kd = 6.8 and 4.8 nM, respectively). The regional distribution of [3H]SR 142948A binding in the rat brain closely matched the distribution of [125I]neurotensin binding. In conclusion, these findings indicate that [3H]SR 142948A is a new potent antagonist radioligand which recognizes with high affinity both neurotensin NT1 and NT2 receptors and represents thus an excellent tool to study neurotensin receptors in the rat brain.
Document type :
Journal articles
Complete list of metadata

Cited literature [42 references]  Display  Hide  Download
Contributor : Catalina Betancur <>
Submitted on : Tuesday, April 29, 2008 - 2:06:30 PM
Last modification on : Monday, December 14, 2020 - 9:45:21 AM
Long-term archiving on: : Friday, May 28, 2010 - 6:00:22 PM


  • HAL Id : inserm-00276332, version 1
  • PUBMED : 9551716


Catalina Betancur, Maryse Canton, Alain Burgos, Bernard Labeeuw, Danielle Gully, et al.. Characterization of binding sites of a new neurotensin receptor antagonist, [3H]SR 142948A, in the rat brain.. European Journal of Pharmacology, Elsevier, 1998, 343 (1), pp.67-77. ⟨inserm-00276332⟩



Record views


Files downloads