Neurotensin receptor

Vincent JP, Mazella J, Kitabgi P (1999) Neurotensin and neurotensin receptors. Trends Pharmacol Sci 20 302-309... 

Kitabgi P (2002) Targeting neurotensin receptors with agonists and antagonists for therapeutic purposes. Curr Opin Drug Discov Devel 5 764—776... 

D. J., Douglas C. L, Boules M., Stewart J.A., Zhao L., Lacy B., Cusack B., Fauq A., Richelson E. Peptide nucleic acids targeted to the neurotensin receptor and administered i.p. cross the blood-brain barrier and specifically reduce gene expression. Proc. Natl Acad. Sci. USA 1999 96 7053-7058. 

Quirion, R. Chiueh. C. Everist, H. and Pert, A. Comparative loealization of neurotensin receptors on nigrostriatal and mesolimbic dopaminergie terminals. Brain Res 327 385-389, 1985. 

As Shown in table 2, a comparative dose of 10 n units of PCP-like activity inhibited 3H-PCP binding in rat brain membranes, but did not inhibit binding of 3 H - d i hydromorphi ne, 3H - D - a 1 a2 - D -1 eu5-enkephalin, 3H-ethylketocyclazocine, 3H-diazepam, or -neurotensin. These results indicate that the active material is specific and selective from PCP receptors, as binding to the mu, delta, and kappa opioid receptors was unaffected, as was binding to benzodiazepine and neurotensin receptors. 

PD149163 Agonist of central neurotensin receptors Interacts with central dopamine systems Potential for treatment of schizophrenia and Parkinson s disease... 

Meclinertant Antagonist of central and peripheral neurotensin receptors Blocks some central and peripheral (vasodilator) actions of neurotensin None identified... 

Three subtypes of neurotensin receptors designated NTi, NT2, and NT3 have been cloned. NTi and NT2 receptors belong to the G protein-coupled superfamily NT3 receptors are structurally different. 

Neurotensin receptors can be blocked with the nonpeptide antagonists SR142948A and SR48692. SR142948A is a potent antagonist of the hypothermia and analgesia produced by centrally administered neurotensin. It also blocks the cardiovascular effects of systemic neurotensin. 

As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exist in nature. A new palladium catalyzed reaction has been recently developed in which bis(pinacolato)diborane(4) mediated the process to reach such a structural motif. The reaction consists of a domino process involving a Miyaura s arylboronic ester synthesis and an intramolecular Suzuki-coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 273, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 53).141... 

The dendrites and axon terminals of midbrain dopaminergic neurons are endowed with CCK and neurotensin receptors (see for review Kalivas, 1993). As emphasized by Smith and Kieval (2000), such findings indicate that these neuropeptides can modulate the spontaneous activity or DA-containing neurons and/or control DA release in their targets. 

Whether neurotensin acts directly at NTRi receptors on TIDA neurons is not clear. The presence of dense neurotensin binding sites located within the mediobasal hypothalamus (Goedert et al., 1985 Meister et al., 1989) and the observation that single unit activity of approximately 70% of all DM-ARC neurons is stimulated by neurotensin in vitro suggest a localized action on (or near) TIDA neurons (Lin and Pan, 1993). Moreover, the presence of synaptic connections between neurotensin-IR and TH-IR neurons in the DM-ARC is consistent with a direct action of neurotensin on TIDA neurons (Marcos et al., 1996a). On the other hand, TIDA neurons do not normally express appreciable amounts of neurotensin receptor mRNA like mesotelencephalic DA neurons... 

Nicot et al., 1995b), and there is very little overlap between the distribution of mRNAs for TH and neurotensin receptors in the DM-ARC or adjacent periventricular nucleus (Nicot et al., 1995b). Collectively, these results suggest that the stimulatory actions of neurotensin on TIDA neurons is not due to a direct action per se, but rather to activation of excitatory interneurons within the ARC. 

Alexander MJ (1997) Dopamine neurons in the adult rat diencephalon express mRNA encoding high-affinity neurotensin receptor. Soc Neurosci Abstr 23 1488. 

Boudin H, Pelaprat D, Rostene W, Beaudet A (1996) Cellular distribution of neurotensin receptors in rat brain immunohistochemical study using an anti-peptide antibody against the cloned high affinity receptor. J Comp Neurol 373 76-89. 

Goedert M, Lightman SL, Mantyh PW, Hunt SP, Emson PC (1985) Neurotensin-like immunoreactivity and neurotensin receptors in the rat hypothalamus and in the neurointermediate lobe of the pituitary gland. Brain Res 358 59-69. 

Kitabgi P, Checler F, Mazella J, Vincent JP (1985) Pharmacology and biochemistry of neurotensin receptors. 

Mazella J, Poustis C, Labbe C, Checler F, Kitabgi P, Granier C, Van Rietschoten J, Vincent J-P (1983) Monoiodo-[Trpll]neurotensin, a highly radioactive ligand of neurotensin receptors. J Biol Chem 255 3476-3481. 

Mazella J (2001) Sortilin/neurotensin receptor-3 a new tool to investigate neurotensin signaling and cellular... 

Navarro V, Martin S, Sarret P, Nielsen MS, Petersen CM, Vincent J-P, Mazella J (2001) Pharmacological properties of the mouse neurotensin receptor 3. Maintenance of cell surface receptor during internalization of neurotensin. FEBS Letts 495.T00-105. 

Nicot A, Rostene W, Berod A (1994) Neurotensin receptor expression in the rat forebrain a combined analysis by in situ hybridization and receptor autoradiography. J Comp Neurol 347407 119. 

Nicot A, Rostene W, Berod A (1995b) Differential expression of neurotensin receptor mRNA in the dopaminergic cell groups of the rat diencephalon and mesencephalon. J Neurosci Res 40 667-674. 

Schotte A, Rostene W, Laudron PM (1988) Different subcellular localization of neurotensin-receptor and neurotensin-acceptor sites in the rat brain dopaminergic system. J Neurochem 50 1026-1031. 

Vincent J-P (1995) Neurotensin receptors binding properties, transduction pathways, and structure. Cell Mol Neurobiol 75 501-511. 

Watson MA, Yamada M, Yamada M, Cusack B, Veverka K, Bolden-Watson C, Richelson E (1992) The rat neurotensin receptor expressed in Chinese hamster ovary cells mediates the release of inositol phosphates. J Neurochem 59 1967-1970. 

Yamada M, Yamada M, Watson MA Richelson E (1993) Neurotensin stimulates cyclic AMP formation in CHO-rNTR-10 cells expressing the cloned rat neurotensin receptor. Eur J Pharmacol 244 99-101. 

NeuNac, A-acetylneuraminic acid (sialic),. /V-acetylneurarriirioside (sialoside), jV-acetylneuraminosyl acid (sialosyl) NEUT, neurotensin NEUT-R, neurotensin receptor NFkB, nuclear factor kB NEAT, nuclear factor of activated T cells NGF, nerve growth factor NGF-RTK, nerve growth factor receptor tyrosine kinase... 

Pettibone DJ, Hess JF, Hey PJ, Jacobson MA, Leviten M, Lis EV, MaUoiga PJ, Pascarella DM, Snyder MA, Williams JB, Zeng Z (2(X)2) The effects of deleting the mouse neurotensin receptor NTRl on central and peripheral responses to neurotensin. J Pharmacol Exp Ther 3(X) 305-313... 

Sarret P, Esdaile MJ, Perron A, Martinez J, Stroh T, Beaudet A (2005) Potent spinal analgesia elicited through stimulation of NTS2 neurotensin receptors. J Neurosci 25 8188-8196... 

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