Objectif To analyze the mechanisms underlying the release of nucleotides from the CNS and target areas.To identify new P2-purinoceptor subtypes and to synthesize novel P2 receptor subtype ligands, expected to be specific agonists/antagonists.To investigate the cellular responses to nucleotides and the intracellular signalling cascades in select examples of neural or glial cells.To characterize the enzymes involved in the extracellular hydrolysis of ATP and ADP.To reveal the pathological implications of extracellular nucleotides, with particular emphasis on nociception. Nucleotides, a novel group of signalling substances in the central and peripheral nervous system will be studied. These include ATP, ADP, UTP or the diadenosine polyphosphates Ap3A, Ap4A, Ap5A, and Ap6A. The release of ATP from nerve endings will be characterized including its function via presynaptic receptors as an autocrine substance. The action of nucleotides on their receptors and the induction of intracellular signalling pathways will be studied in select examples such as astrocytes and the sensory hair cells of the inner ear. This includes the differentiation by selective analogues between the various nucleotide receptor subtypes including those for nucleoside 5'-triphosphates and the diadenosine polyphosphates. New P2-receptor subtypes will be identified and isolated. The involvement of ATP and possibly other nucleotides in pathological mechanisms is investigated using nociception as an example. The enzymes that effect the extracellular hydrolysis of nucleotides such as ATP and ADP are characterized in functional and molecular terms. Their sites of expression in the nervous system will be determined using immunocytochemistry. Analogues are developed that differentiate between nucleotide receptor subtypes and that selectively affect either receptors or ecto-nucleotidase. These substances will be the basis for the development of drugs to deal with diseases based on specific faults in the signalling cascade via extracellular nucleotides. Champ scientifique sciences naturellessciences biologiquesneurobiologiesciences naturellessciences biologiquesbiologie cellulairesignalisation cellulairesciences naturellessciences biologiquesgénétiquenucléotidesciences naturellessciences biologiquesbiochimiebiomoléculeprotéinesenzyme Programme(s) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Thème(s) 3.1 - Pathophysiology and basic mechanisms Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur Johann-Wolfgang-Goethe Universität Frankfurt Adresse 9,marie-curie-strasse 60439 Frankfurt-am-main Allemagne Voir sur la carte Contribution de l’UE Aucune donnée Participants (6) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire Albert-Ludwigs-Universität Freiburg Allemagne Contribution de l’UE € 0,00 Adresse 5,hermann-herder-strasse 79104 Freiburg Voir sur la carte Autres sources de financement Aucune donnée Stockholms Universitet Suède Contribution de l’UE € 0,00 Adresse 21 a,stockholm university 106 91 Stockholm Voir sur la carte Autres sources de financement Aucune donnée THE UNIVERSITY OF MILANO Italie Contribution de l’UE € 0,00 Adresse Via balzaretti 9 20133 Milano Voir sur la carte Autres sources de financement Aucune donnée Universidad Complutense de Madrid Espagne Contribution de l’UE € 0,00 Adresse S/n,universidad complutense 2840 Madrid Voir sur la carte Autres sources de financement Aucune donnée Universidade de Lisboa Portugal Contribution de l’UE € 0,00 Adresse Avenida prof. egas moniz 1600 Lisboa Voir sur la carte Autres sources de financement Aucune donnée University College London Royaume-Uni Contribution de l’UE € 0,00 Adresse 5,rowland hill street NW3 2PF London Voir sur la carte Autres sources de financement Aucune donnée
