The first part of the research is devoted to mechanistic insight into the nature of direct Zn interactions with 5 HT1A receptors, investigated with in vitro radioligand experiments and functional assays. The influence of Zn ions on agonist binding was measured by saturation, competition and both association and dissociation kinetic studies using [3H]8-OH-DPAT, also in the functional tests. The obtained results showed zinc non-competitive interactions toward agonist binding site of serotonin 5 HT1A receptors. The biphasic effects, involving potentiation of both agonist binding and function at sub-micromolar concentrations of zinc ions along with the inhibition of agonist affinity at sub-millimolar zinc concentrations, were observed.
In the second part of the thesis, I focus on 5-HT7 receptors. As a result of the research, zinc allosteric inhibition of both agonist and antagonist binding was observed in radioligand binding studies, as well as zinc neutral antagonism at the concentration of 10 μM in the functional assay. Given that zinc potentiation of agonist activity at 5-HT1A receptors and its inhibiting properties on 5-HT7 receptors signaling were detected at low concentrations of zinc ions, it could be hypothesized that these effects may represent the most likely direction of zinc activity under physiological conditions.
May 24, 2021
Mar 29, 2018
|ZB-127777||May 24, 2021|