Objetivo To examine the role of each metabotropic glutamate receptor (mGluR) subtype in physiology To examine the role of each mGluR subtype in selected neuropathological models . To develop selective agonists and antagonists of mGluRs.Functional properties of neuronal populations expressing diverse mGluR subtypes will be studied by utilising electrophysiological, biochemical and anatomical techniques. The presynaptic mechanisms whereby mGluR subtypes control neurotransmitter release or the activity of ligand-gated or voltage-operated channels will be evaluated. Molecular biology studies with mGluR chimeras or transfected cells expressing mGluRs will identify critical domains responsible for their specific properties. Finally, attempts to correlate electrophysiological observations with behavioural tasks will also be performed.Gene expression, pharmacology and electrophysiology of mGluRs will be studied in models of cerebral ischemia in vitro and in vivo and in epilepsy. Behavioural (motor and learning), electrophysiological and biochemical abnormalities will be evaluated in transgenic mice lacking specific mGluRs and in animals treated with antisense oligonucleotides directed against mGluR mRNAs or with selective mGluR subtype antagonists, when developed. We expect to clarify the role played by mGluRs in these pathologies, and whether their activation or blockade might become potentially useful in clinical practice.Preliminary experiments indicate that aminoindane dicarboxylates (conformationally restricted analogues of phenylglycines) may selectively interact with mGluR subtypes with IC50S in the micromolar range. These compounds were synthesised and patented by three groups participating in this Project and they will be made available to other groups and tested. Since a higher degree of selectivity and affinity are still needed for mGluR research, in the course of this Project new molecules will be designed, synthesised and studied. Upon completion of the Project, novel pharmacological tools will be made available to the scientific community, as well as molecules which might be developed as drugs. Ámbito científico medical and health sciencesbasic medicineneurologyepilepsymedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologymedical and health sciencesbasic medicinepharmacology and pharmacynatural sciencesbiological sciencesmolecular biology Programa(s) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Tema(s) 1.1 - Pharmacotoxicology Convocatoria de propuestas Data not available Régimen de financiación CSC - Cost-sharing contracts Coordinador UNIVERSITY OF FLORENCE Aportación de la UE Sin datos Dirección Viale G. Pieraccini 6 50139 FIRENZE Italia Ver en el mapa Coste total Sin datos Participantes (9) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo Centre National de la Recherche Scientifique Francia Aportación de la UE Sin datos Dirección CCIPE, RUE DE LA CARDONILLE 34094 MONTPELLIER Ver en el mapa Coste total Sin datos Federal Institute for Neurobiology Alemania Aportación de la UE Sin datos Dirección 6,Brenneckestrasse 6 39008 MAGDEBURG Ver en el mapa Coste total Sin datos Novo-Nordisk A/S Dinamarca Aportación de la UE Sin datos Dirección NOVO NORDISK PARK 2760 MALOV Ver en el mapa Coste total Sin datos Rijksuniversiteit Utrecht Países Bajos Aportación de la UE Sin datos Dirección 100,Universiteitsweg 3584 CG UTRECHT Ver en el mapa Coste total Sin datos Universidad Complutense de Madrid España Aportación de la UE Sin datos Dirección S/N,AVDA. PUERTA DE HIERRO S/N 28040 MADRID Ver en el mapa Coste total Sin datos University of Bristol Reino Unido Aportación de la UE Sin datos Dirección UNIVERSITY WALK BS8 1TD BRISTOL Ver en el mapa Coste total Sin datos University of Dublin Irlanda Aportación de la UE Sin datos Dirección 2 DUBLIN Ver en el mapa Coste total Sin datos University of Dundee Reino Unido Aportación de la UE Sin datos Dirección Ninewells Hospital & Med. School DD1 9SY DUNDEE Ver en el mapa Coste total Sin datos Università degli Studi di Perugia Italia Aportación de la UE Sin datos Dirección Via del Liceo 1 06123 Perugia Ver en el mapa Coste total Sin datos