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Characterization and distribution of binding sites for a new neurotensin receptor antagonist ligand, [3H]SR 48692, in the guinea pig brain.

Abstract : SR 48692, a selective nonpeptide antagonist of neurotensin (NT) receptors was developed recently. In the present work we studied the binding properties of the corresponding radioligand, [3H]SR 48692, in the adult guinea pig brain. The characterization of [3H]SR 48692 binding was carried out on brain membrane preparations and the distribution of [3H]SR 48692 binding sites was determined by receptor autoradiography and compared to that of [125I]NT binding sites. In brain homogenates, [3H]SR 48692 bound to a single population of sites with a Kd of 2.19 nM and a maximal binding capacity of 1.15 pmol/mg of protein. This maximal binding capacity value was 20 times higher than that observed for [125I]NT. NT agonists were able to interact competitively with the entire population of binding sites labeled by [3H]SR 48692, but their affinities were much lower than those observed for [125I]NT. By contrast, NT antagonists exhibited similar abilities to inhibit the binding of both radioligands. The addition of unlabeled NT in saturation assays revealed a competitive inhibition of [3H]SR 48692 binding, suggesting that agonist and antagonist ligand bind to overlapping domains of the NT receptor. The autoradiographic distribution of the low-affinity NT binding sites detected by [3H]SR 48692 (96% of the receptors) was very similar to the distribution of high-affinity receptors labeled with [125I]NT (4% of the receptors). In addition, the binding of [3H]SR 48692 was insensitive to guanyl nucleotides. Taken together, these findings suggest that the binding sites detected by [3H]SR 48692 in the guinea pig brain mainly represent the uncoupled form of the NT receptor.
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Contributor : Catalina Betancur <>
Submitted on : Tuesday, April 29, 2008 - 9:54:29 PM
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Catalina Betancur, Maryse Canton, Danielle Gully, Gema Vela, Didier Pélaprat, et al.. Characterization and distribution of binding sites for a new neurotensin receptor antagonist ligand, [3H]SR 48692, in the guinea pig brain.. Journal of Pharmacology and Experimental Therapeutics, American Society for Pharmacology and Experimental Therapeutics, 1995, 273 (3), pp.1450-8. ⟨inserm-00276482⟩



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