Neuronoprotective action of cortexin andcortagen

Abstract

The changes of both intracellular resting potential and action potential of the identified neurons of pedal ganglia of the mollusk Planorbarius corneus CNS registered by means of intracellular microelectrodes, and ionic currents of isolated neurons under fixed potential after administration of officinal peptide drug cortexine (cortexine 0.5–1000 µg/ ml and glycine 4–4000 µM), cortexine peptides (0.5–1000 µg/ ml), glycine (0.5 and 5 µM) and tetrapeptide cortagen (0.1–10000 µM) were studied. Both the drug cortexine and cortexine peptides were shown to modulate the electrical activity of neurons by the same manner: moderately changed the resting potential, the action potential and impulse frequency that was interpreted as activating action. Glycine activated neuronal activity as cortexine but in less degree. The mixture of cortexine and glycine (drug cortexine) did not inhibit and did not disturb the functional state of neurons of action, and the hyperpolarization was always observed after administration of peptides as well as the shortening of the action potential, increase of their amplitude and reduction of impulse frequency of neurons. Tetrapeptide cortagen in concentrations 0.1–100 µM also hyperpolarized neurons by 2–3 mV and reduced their spontaneous activity that indicated on its activating (neuronoprotective) action. Cortagen in concentration 1000 µM depolarized the neurons moderately (by 2–4 mV), the increase of impulse activity was registered, and in concentration 10 mM it depolarized neurons significantly and reversible, increasing the frequency and inhibiting the generation of the action potential. Cortagen activated neurons in more degree than cortexine. Cortagen in concentration 0.1 µM also increased the amplitude of slow efflux current by 3–5 %. We did not observe the increased amplitude (activation) of influx sodium and calcium channels after administration of cortagen. A dose-dependent and reversible inhibition of amplitudes of these currents began after administration of cortagen in concentrations 100 µM and more up to 80–90 % inhibition after peptide concentration 10 mM. The inhibition of sodium channels was more intensive than calcium channels. These effects of action of the peptide administered in high concentrations can be qualified as nonspecific and toxic ones.