Cellular and Receptor Mechanisms of Action of Nootropic and Neuroprotective Peptides Used in Clinical Practice

• Published in: Human physiology 2021-12, Vol.47 (8), p.870-877
• Main Authors: Kolbaev, S. N., Sharonova, I. N., Skrebitsky, V. G.
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors; Acetylcholine receptors (nicotinic); Biomedical and Life Sciences; Biomedicine; Calcium (intracellular); Calcium signalling; Choline; Cholinergic transmission; Cognitive enhancement; Hippocampus; Human Physiology; Life Sciences; Metabotropic receptors; Neurons; Neuroprotection; Receptor mechanisms; Stratum radiatum
• ISSN: 0362-1197; 1608-3164
• DOI: 10.1134/S0362119721080077

This study investigated the effect of the original nootropic and neuroprotective agent Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) on changes in the intracellular concentration of calcium ions ([Ca 2+ ] i ). Experiments on freshly prepared slices of the rat hippocampus showed that the presence of Noopept (1 µM) stimulates spontaneous changes in the [Ca 2+ ] i in neurons of both the stratum pyramidale and stratum radiatum of the CA1 region. There was a significant increase in the amplitude and duration of the recorded calcium signals, as well as a noticeable increase in the percentage of active neurons. The frequency of spontaneous short-term increases in [Ca 2+ ] i also increased significantly in the stratum pyramidale. To assess the modulating effect of Noopept on cholinergic transmission, we studied the changes in calcium ion entry during activation of the α7 nicotinic acetylcholine receptor (α7 nAChR). Local application of choline, a selective α7 nAChR agonist, caused a brief (2–10 s) increase in [Ca 2+ ] i in the neurons of the stratum radiatum, while responses in the stratum pyramidale neurons occurred only sparsely. There were no significant changes in the amplitude of responses to choline in the presence of Noopept. In electrophysiological experiments (patch clamp method), local application of choline caused current generation in the stratum radiatum (but not pyramidale) neurons, the amplitude of which was also not affected by Noopept. Although these observations do not support the hypothesis that Noopept can directly modulate α7 acetylcholine receptors, they do not exclude Noopept’s enhancement of the metabotropic component associated with their activation. Therefore, the data obtained by optical recording confirm the modulating effect of Noopept on hippocampal neuron activity, which is manifested as the increased amplitude and duration of calcium transients in neurons of different layers.