title: Effects of the neuropeptide Y Y(2) receptor antagonist BIIE0246 on presynaptic inhibition by neuropeptide Y in rat hippocampal slices.
abstract: We previously reported that (S)-N(2)-[[1-[2-[4-[(R,S)-5, 11-dihydro-6(6h)-oxodibenz[b, e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl]cylopentyl]a cetyl]-N-[2-[1, 2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2, 4-triazol-4-yl]ethyl]argininamid, BIIE0246, is a potent and highly selective neuropeptide Y Y(2) receptor antagonist. Neuropeptide Y Y(2) receptors have been proposed to mediate the inhibition by neuropeptide Y of excitatory synaptic transmission in rat hippocampus. Therefore, we investigated the effects of BIIE0246 on the electrophysiological properties of neuropeptide Y in rat hippocampal slices and determined the affinity of this novel antagonist for rat hippocampal neuropeptide Y Y(2) receptors. BIIE0246 displayed an affinity of IC(50)=4.0+/-1.6 (n=4) for neuropeptide Y receptor binding sites labelled by 125I-neuropeptide Y in rat hippocampal membranes. At a concentration of 1 microM, BIIE0246 completely antagonized the inhibitory effects of 300 nM neuropeptide Y on synaptic transmission in rat hippocampal slices. This is the first study showing that a selective neuropeptide Y Y(2) receptor antagonist is able to block neuropeptide Y mediated effects in the hippocampus and unambiguously characterizes the presynaptic receptor in the rat hippocampus as the neuropeptide Y Y(2) receptor.
authors.affiliation: Boehringer Ingelheim Pharma KG, 55216 Ingelheim, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Weiser
authors.forename: H A
authors.initials: HA
authors.lastname: Wieland
authors.forename: H N
authors.initials: HN
authors.lastname: Doods
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D001667:Binding, Competitive; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D017661:Receptors, Presynaptic / Q000037:antagonists & inhibitors*; D013569:Synapses / Q000187:drug effects
chemical_list: D001552:Benzazepines; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D017661:Receptors, Presynaptic; C095889:neuropeptide Y2 receptor; D001120:Arginine; C403256:BIIE 0246