title: Blockade of neurotensin receptors by the antagonist SR 48692 partially prevents retrograde axonal transport of neurotensin in rat nigrostriatal system.
abstract: The effect of SR 48692, a potent and selective non-peptide antagonist of the neurotensin receptor, was investigated on the retrograde axonal transport of neurotensin in the rat nigrostriatal dopamine pathway. When rats were injected in the striatum with (3-[125I]iodotyrosyl3)neurotensin, a substantial accumulation of radioactivity appeared in the ipsilateral substantia nigra 1.5 h after injection, and highest levels (336 +/- 23 dpm/mg of protein) were observed 2.5-3.5 h after the injection. The phenomenon required a pretreatment of the animals with thiorphan (30 micrograms) an inhibitor of endopeptidase. The amount of radioactivity accumulated (3.5 h) was found to be reduced (25%) by local (100 nM) or peripheral administration of SR 48692 (5, 10, 20 mg/kg, i.p.; 25%, 40%, 40%, respectively). Our results indicate that blockade of neurotensin receptors by a selective non-peptide receptor antagonist affects the retrograde axonal transport of the tridecapeptide, and further suggest the notion that this process involves neurotensin receptors.
authors.affiliation: Sanofi Recherche, Neuropsychiatry Department, Montpellier, France.
authors.forename: R
authors.initials: R
authors.lastname: Steinberg
authors.forename: I
authors.initials: I
authors.lastname: Bougault
authors.forename: J
authors.initials: J
authors.lastname: Souilhac
authors.forename: D
authors.initials: D
authors.lastname: Gully
authors.forename: G
authors.initials: G
authors.lastname: Le Fur
authors.forename: P
authors.initials: P
authors.lastname: Soubrié
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C086487:SR 48527; C079087:SR 48692; D009496:Neurotensin; D004298:Dopamine