Biomaterial Database

Effects of the neuropeptide Y Y(2) receptor antagonist BIIE0246 on presynaptic inhibition by neuropeptide Y in rat hippocampal slices. 2000

T Weiser, and H A Wieland, and H N Doods

Boehringer Ingelheim Pharma KG, 55216 Ingelheim, Germany.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009433	Neural Inhibition	The function of opposing or restraining the excitation of neurons or their target excitable cells.	Inhibition, Neural
D009478	Neuropeptide Y	A 36-amino acid peptide present in many organs and in many sympathetic noradrenergic neurons. It has vasoconstrictor and natriuretic activity and regulates local blood flow, glandular secretion, and smooth muscle activity. The peptide also stimulates feeding and drinking behavior and influences secretion of pituitary hormones.	Neuropeptide Y-Like Immunoreactive Peptide,Neuropeptide Tyrosine,Neuropeptide Y Like Immunoreactive Peptide,Tyrosine, Neuropeptide
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001120	Arginine	An essential amino acid that is physiologically active in the L-form.	Arginine Hydrochloride,Arginine, L-Isomer,DL-Arginine Acetate, Monohydrate,L-Arginine,Arginine, L Isomer,DL Arginine Acetate, Monohydrate,Hydrochloride, Arginine,L Arginine,L-Isomer Arginine,Monohydrate DL-Arginine Acetate
D001552	Benzazepines	Compounds with BENZENE fused to AZEPINES.
D001667	Binding, Competitive	The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.	Competitive Binding
D013569	Synapses	Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.	Synapse