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The project is dedicated on the studies of the mechanisms of the functioning of heptahelix receptors and their regulatory proteins, which are key players in chemical signal transduction in nervous system. It includes studies on physico-chemical recognition processes of ligand binding on receptors and mechanisms of generation second messengers to elaborate kinetic and structural models of ligand-receptor-G protein-nucleotide complexes. It will be based on the comparison of properties of different receptors (monoaminergics, peptic, steroid) determined by the influence of physical (temperature, fluidity of membranes), chemical (Me ions, nucleotides, structure of ligands) and biochemical (receptor oligomerization, regulatory proteins) factors on the ability to bind specific ligands and on the ability to form complexes with different G proteins and generate secondary messengers. Special attention will be paid on the regulatory mechanisms causing hypo- and hyperactivity of signal transduction of monoamine receptors in the brain in the case of differently behaving animals and their pathologies. There will be elaborated and validated methods for correct measurement of interactions of ligands with receptors and their ability to modulate physiological response. Special attention will be paid on the implementation of non-radioactive methods of determination of receptor properties. |