Structure, Functional Expression, and Cerebral Localization of the Levocabastine-sensitive Neurotensin/neuromedin N Receptor from Mouse Brain

Overview

Journal J Neurosci

Specialty Neurology

Date 1996 Sep 15

PMID 8795617

Citations 58

Authors

J Mazella

J M Botto

E Guillemare

T Coppola

P Sarret

J P Vincent

Affiliations

Soon will be listed here.

Abstract

This work describes the cloning and expression of the levocabastine-sensitive neurotensin (NT) receptor from mouse brain. The receptor protein comprises 417 amino acids and bears the characteristics of G-protein-coupled receptors. This new NT receptor (NTR) type is 39% homologous to, but pharmacologically distinct from, the only other NTR cloned to date from the rat brain and the human HT29 cell line. When the receptor is expressed in Xenopus laevis oocytes, the H1 antihistaminic drug levocabastine, like NT and neuromedin N, triggers an inward current. The pharmacological properties of this receptor correspond to those of the low-affinity, levocabastine-sensitive NT binding site described initially in membranes prepared from rat and mouse brain. It is expressed maximally in the cerebellum, hippocampus, piriform cortex, and neocortex of adult mouse brain.

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References

Baldwin J . The probable arrangement of the helices in G protein-coupled receptors. EMBO J. 1993; 12(4):1693-703. PMC: 413383. DOI: 10.1002/j.1460-2075.1993.tb05814.x. View

Feurle G, Hamscher G, Kusiek R, Meyer H, Metzger J . Identification of xenin, a xenopsin-related peptide, in the human gastric mucosa and its effect on exocrine pancreatic secretion. J Biol Chem. 1992; 267(31):22305-9. View

Vita N, Laurent P, Lefort S, Chalon P, Dumont X, Kaghad M . Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor. FEBS Lett. 1993; 317(1-2):139-42. DOI: 10.1016/0014-5793(93)81509-x. View

Dobner P, Barber D, McKiernan C . Cloning and sequence analysis of cDNA for the canine neurotensin/neuromedin N precursor. Proc Natl Acad Sci U S A. 1987; 84(10):3516-20. PMC: 304902. DOI: 10.1073/pnas.84.10.3516. View

Kozak M . An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987; 15(20):8125-48. PMC: 306349. DOI: 10.1093/nar/15.20.8125. View

Dubuc I, Costentin J, Terranova J, Barnouin M, Soubrie P, Le Fur G . The nonpeptide neurotensin antagonist, SR 48692, used as a tool to reveal putative neurotensin receptor subtypes. Br J Pharmacol. 1994; 112(2):352-4. PMC: 1910364. DOI: 10.1111/j.1476-5381.1994.tb13077.x. View

Pettibone D, TOTARO J, Harris E, ROBINSON F . Heterogeneity of [3H]neurotensin bindings: studies with dynorphin, L-156,903 and levocabastine. Brain Res. 1988; 457(2):212-8. DOI: 10.1016/0006-8993(88)90688-9. View

Palacios J, Pazos A, Dietl M, Schlumpf M, Lichtensteiger W . The ontogeny of brain neurotensin receptors studied by autoradiography. Neuroscience. 1988; 25(1):307-17. DOI: 10.1016/0306-4522(88)90028-0. View

Chabry J, Labbe-Jullie C, Gully D, Kitabgi P, Vincent J, Mazella J . Stable expression of the cloned rat brain neurotensin receptor into fibroblasts: binding properties, photoaffinity labeling, transduction mechanisms, and internalization. J Neurochem. 1994; 63(1):19-27. DOI: 10.1046/j.1471-4159.1994.63010019.x. View

10.

Gully D, Canton M, Boigegrain R, Jeanjean F, Molimard J, Poncelet M . Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor. Proc Natl Acad Sci U S A. 1993; 90(1):65-9. PMC: 45600. DOI: 10.1073/pnas.90.1.65. View

11.

Lomasney J, Lorenz W, Allen L, King K, Regan J, Yang-Feng T . Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2. Proc Natl Acad Sci U S A. 1990; 87(13):5094-8. PMC: 54268. DOI: 10.1073/pnas.87.13.5094. View

12.

Mazella J, Poustis C, Labbe C, Checler F, Kitabgi P, Granier C . Monoiodo-[Trp11]neurotensin, a highly radioactive ligand of neurotensin receptors. Preparation, biological activity, and binding properties to rat brain synaptic membranes. J Biol Chem. 1983; 258(6):3476-81. View

13.

KYTE J, Doolittle R . A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982; 157(1):105-32. DOI: 10.1016/0022-2836(82)90515-0. View

14.

SCHOTTE A, Laduron P . Different postnatal ontogeny of two [3H]neurotensin binding sites in rat brain. Brain Res. 1987; 408(1-2):326-8. DOI: 10.1016/0006-8993(87)90398-2. View

15.

Kong H, Raynor K, Yasuda K, Bell G, Reisine T . Mutation of an aspartate at residue 89 in somatostatin receptor subtype 2 prevents Na+ regulation of agonist binding but does not alter receptor-G protein association. Mol Pharmacol. 1993; 44(2):380-4. View

16.

Masu Y, Nakayama K, Tamaki H, Harada Y, Kuno M, Nakanishi S . cDNA cloning of bovine substance-K receptor through oocyte expression system. Nature. 1987; 329(6142):836-8. DOI: 10.1038/329836a0. View

17.

SCHOTTE A, Leysen J, Laduron P . Evidence for a displaceable non-specific [3H]neurotensin binding site in rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1986; 333(4):400-5. DOI: 10.1007/BF00500016. View

18.

Labbe-Jullie C, Dubuc I, Brouard A, Doulut S, Bourdel E, Pelaprat D . In vivo and in vitro structure-activity studies with peptide and pseudopeptide neurotensin analogs suggest the existence of distinct central neurotensin receptor subtypes. J Pharmacol Exp Ther. 1994; 268(1):328-36. View

19.

Vincent J . Neurotensin receptors: binding properties, transduction pathways, and structure. Cell Mol Neurobiol. 1995; 15(5):501-12. PMC: 11563118. DOI: 10.1007/BF02071313. View

20.

Probst W, Snyder L, Schuster D, Brosius J, Sealfon S . Sequence alignment of the G-protein coupled receptor superfamily. DNA Cell Biol. 1992; 11(1):1-20. DOI: 10.1089/dna.1992.11.1. View