Z-Project (coordination and central funds)

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P2 receptors in the peripheral and central nervous system are targets of extracellular nucleotides. Especially ATP/ADP and UTP/UDP are important signalling molecules. Our consortium will investigate ligand-gated P2X and G protein-coupled P2Y receptors at neurons, glial cells and their common precursor cells. We intend to elucidate the structure, assembly, transduction pathways and interaction mechanisms of these receptors. The structural pre-requisites for ligand-binding or agonist promiscuity will be clarified. Transgenic mice will be generated to facilitate the visual identification and mapping of the relevant receptor classes as well as to study their up- or down-regulation and their accessory proteins. We will also carry out functional studies on a few selected cell systems (sensory neurons, astrocytes, Müller cells, microglia) where P2X and/or P2Y receptors may play important roles in the development of e.g. neuropathic pain, retinal damage, Parkinson¿s disease or neurodegenerative illnesses. A wide methodological competence is available to approach the targeted aims. The already mentioned transgenic animals generated by the members of the Research Unit and additional knockout mice obtained from external sources will be used collectively. The projects will either be carried out at the Medical Faculty of the University of Leipzig or they will be intimately associated with this Faculty. It is intended to establish in Leipzig a nationwide center for coordinating German P2 receptor research.