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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.
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https://www.hal.inserm.fr/inserm-00276332
Contributor : Catalina Betancur <>
Submitted on : Tuesday, April 29, 2008 - 2:06:30 PM
Last modification on : Friday, December 14, 2018 - 1:27:00 AM
Long-term archiving on: : Friday, May 28, 2010 - 6:00:22 PM

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

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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⟩

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