Molecular cloning of a levocabastine‐sensitive neurotensin binding site

A search for sequences homologous to the neurotensin receptor cDNA in a rat hypothalamic library has identified a novel neurotensin receptor (NTR‐2). The 1539 bp cDNA encodes a 416 amino acid protein and shows highest homology to the previously cloned neurotensin receptor (NTR‐1) (64% homology and 43% identity). Binding and pharmacological studies demonstrate that NTR‐2 expressed in COS cells recognizes neurotensin (NT) with high affinity as well as several other agonists and antagonists. However, a fundamental difference was found; unlike NTR‐1, NTR‐2 recognizes, with high affinity, levocabastine, a histamine H1 receptor antagonist previously shown to compete with NT for low‐affinity binding sites in brain.

[1]  C. Nemeroff The interaction of neurotensin with dopaminergic pathways in the central nervous system: Basic neurobiology and implications for the pathogenesis and treatment of schizophrenia , 1986, Psychoneuroendocrinology.

[2]  P. Soubrié,et al.  SR 48692, a non-peptide neurotensin receptor antagonist differentially affects neurotensin-induced behaviour and changes in dopaminergic transmission , 1994, Neuroscience.

[3]  M. Watson,et al.  Neurotensin stimulates cyclic AMP formation in CHO-rNTR-10 cells expressing the cloned rat neurotensin receptor. , 1993, European journal of pharmacology.

[4]  P. Kitabgi,et al.  Stable Expression of the Cloned Rat Brain Neurotensin Receptor into Fibroblasts: Binding Properties, Photoaffinity Labeling, Transduction Mechanisms, and Internalization , 1994, Journal of neurochemistry.

[5]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[6]  P. Soubrié,et al.  Turning behavior induced by intrastriatal injection of neurotensin in mice: sensitivity to non-peptide neurotensin antagonists , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[7]  W. Rostène,et al.  Neurotensin receptor expression in the rat forebrain and midbrain: A combined analysis by in situ hybridization and receptor autoradiography , 1994, The Journal of comparative neurology.

[8]  J. Maloteaux,et al.  Phospholipase C activation by neurotensin and neuromedin N in Chinese hamster ovary cells expressing the rat neurotensin receptor. , 1992, Brain research. Molecular brain research.

[9]  F. Checler,et al.  Regulation of cyclic GMP levels by neurotensin in neuroblastoma clone N1E115. , 1985, Biochemical and biophysical research communications.

[10]  P. Kitabgi,et al.  Neurotensin stimulates inositol trisphosphate-mediated calcium mobilization but not protein kinase C activation in HT29 cells. Involvement of a G-protein. , 1989, The Biochemical journal.

[11]  M. Watson,et al.  Identification of a polymorphism in the human neurotensin receptor gene. , 1993, Mayo Clinic proceedings.

[12]  P. Soubrié,et al.  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 , 1995, British journal of pharmacology.

[13]  P. Kitabgi,et al.  Neurotensin modulates dopamine neurotransmission at several levels along brain dopaminergic pathways , 1989, Neurochemistry International.

[14]  E. Richelson,et al.  The neurotensin receptor: is there more than one subtype? , 1996, Trends in pharmacological sciences.

[15]  P. Soubrié,et al.  The nonpeptide neurotensin antagonist, SR 48692, used as a tool to reveal putative neurotensin receptor subtypes , 1994, British journal of pharmacology.

[16]  Masayuki Masu,et al.  Structure and functional expression of the cloned rat neurotensin receptor , 1990, Neuron.

[17]  J. Maloteaux,et al.  Interaction of the COOH-terminal domain of the neurotensin receptor with a G protein does not control the phospholipase C activation but is involved in the agonist-induced internalization. , 1996, Molecular pharmacology.

[18]  K. Veverka,et al.  The Rat Neurotensin Receptor Expressed in Chinese Hamster Ovary Cells Mediates the Release of Inositol Phosphates , 1992, Journal of neurochemistry.

[19]  J. Mai,et al.  Neurotensin in the human brain , 1987, Neuroscience.

[20]  S. E. Ruane,et al.  Distribution and immunochemical character of neurotensin-like material in representative vertebrates and invertebrates: Apparent conservation of the COOH-terminal region during evolution , 1982, Peptides.

[21]  P. Laduron,et al.  Different postnatal ontogeny of two [3H]neurotensin binding sites in rat brain , 1987, Brain Research.

[22]  P Ferrara,et al.  Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor , 1993, FEBS letters.