title: Characterization of [(3)H]ucb 30889 binding to synaptic vesicle protein 2A in the rat spinal cord.
abstract: The novel antiepileptic drug levetiracetam ((2S-(2-oxo-1-pyrrolidinyl)butanamide, KEPPRA possesses a specific binding site in brain, which has very recently been identified as the synaptic vesicle protein SV 2 A. The aim of this study was to evaluate the presence of a levetiracetam binding site in the spinal cord and compare its properties to that in rat brain. We used [(3)H]ucb 30889 ((2S)-2-[4-(3-azidophenyl)-2-oxopyrrolidin-1-yl]butanamide), a levetiracetam analogue, to perform binding assays, photoaffinity labelling and autoradiography experiments, and revealed the presence of SV 2 A by Western-blot analysis. [(3)H]ucb 30889 binding kinetics at 4 degrees C were biphasic and saturation binding curves were compatible with the labelling of a homogenous population of binding sites with a K(d) similar to that in brain. Competition curves with ligands known to interact with levetiracetam binding sites and photolabelling experiments indicated that [(3)H]ucb 30889 labels the same 90 kDa protein in both spinal cord and brain. Levetiracetam binding site was localised in the grey matter of the spinal cord and its expression was not modified in a model of neuropathic pain. This study demonstrates the presence of a specific levetiracetam binding site in the rat spinal cord, which is similar to that found in rat brain.
authors.affiliation: UCB S.A., CNS In Vitro Pharmacology, Building R4, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium. athalie.lambeng@ucb-group.com
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lambeng
authors.forename: Michel
authors.initials: M
authors.lastname: Gillard
authors.forename: Pascale
authors.initials: P
authors.lastname: Vertongen
authors.forename: Bruno
authors.initials: B
authors.lastname: Fuks
authors.forename: Pierre
authors.initials: P
authors.lastname: Chatelain
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000378:metabolism*; D001386:Azides / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D000077287:Levetiracetam; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D011759:Pyrrolidines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: C487592:(2S)-2-(4-(3-azidophenyl)-2-oxopyrrolidin-1-yl)butanamide; D000927:Anticonvulsants; D001386:Azides; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines; C489618:Sv2a protein, rat; D000077287:Levetiracetam; D010889:Piracetam