Tsintsadze V. Investigation of synaptic transduction modulation by non-hidrolizeble diadenosine polyphosphate analogue in rat hippocampus.

This dissertation is devoted to the non-hidrolyzable diadenosine polyphosphate analogue (AppCH2ppA) action on synaptic transmission in hippocampus. There were considered AppCH2ppA effects on some hippocampal pathways. Action of this polyphosphate on СА3/СА1-pathway was researched in detail. AppCH2ppA affects postsynaptic membrane excitability and calls for the cascade of events, namely activation purine P2-receptors, nitric oxide release, adenosine synthesis, adenosine binding with postsynaptic А1-receptors and activation of hiperpolarization conductivity. In isolated cells AppCH2ppA showed the ability to modulation of NMDA-current amplitudes. In most cases NMDA-current amplitudes rised in presence of AppCH2ppA, so it was decided to investigate this potentiative effect AppCH2ppA narrowly. Purine receptor blockers modulated this potentiation of NMDA-currents. Bivalent cation chelator EDTA induced potentiation of NMDA-currents as well as AppCH2ppA. Moreover, it was shown that incubation of cells with genestein abolished NMDA-current increasing by AppCH2ppA. Perhaps, AppCH2ppA bind with purine receptors and activate it. This leads to tyrosine kinase activation. Tyrosine kinase modulates NMDA-receptor functions and decreases affinity to zinc ions.