Using intracellular recording, we studied the effects of N-uronoyl derivatives of an amino acid and peptides (1,2:3,4-di-O-isopropylidene-αa-D-galactopyranuronoyl)-β-alanine (DAGU-Ala), DAGU-glycylglycine (DAGU-Gly-Gly), DAGU-glycyl-D,L-glutamic acid (DAGU-Gly-Glu), as well as of 1,2:3,4-di-О-isopropylidene-αa-D-galactopyranosyluronic acid (DAGU itself), β-alanine (β-Ala), D,L-glutamic acid (D,L-Glu), and glycyl-glycine (Gly-Gly), which were added to the extracellular milieu, on the electrical activity of PPa1 and PPa2 neurons and unidentified neurons of Helix albescens Rossm. DAGU-Gly-Gly applied in concentrations of 10 -4 to 10 -2 М hyperpolarized the membrane in a dose-dependent manner and decreased insignificantly the amplitude of action potentials (APs). Applications of DAGU-Ala, β-Ala, DAGU-Gly-Glu, D,L-Glu, and Gly-Gly in the same doses resulted in a shift of the membrane potential toward depolarization and in a drop in the amplitude of APs. Measurements of the first AP derivatives showed that all the above-mentioned substances suppressed in a concentration-dependent manner both inward and outward transmembrane ion currents. In this case, DAGU suppressed both inward and outward currents, while DAGU-Ala, β-Ala, DAGU-Glu, D,L-Glu, and Gly-Gly inhibited predominantly the outward potassium ion current; DAGU-Gly-Gly inhibited inward sodium and potassium ion currents. Results of a comparative analysis of the neurotropic action of the tested amino acids and their Ν-uronoyl derivatives showed that modification of the molecules of neurotransmitter amino acids leads to a decrease in their neurotoxicity and to an increase in their membranotropic properties.
INTRODUCTIONIn search of ways for modulating functions of the CNS, it was found that derivatives of neuroactive amino acids demonstrate a number of special effects; these derivatives can show new properties dissimilar to those of amino acids. It was, e.g., demonstrated that substitution of an amino group in the structure of neuroactive amino acids with a 4-hydroxy-4-methyl-3-tetrahydropyranyl radical leads to the appearance of psychotropic properties in the synthesized compounds [1]. It was reported that choline ethers of L-alanine, L-valine, and γ-aminobutyric acid exert mild antiseizure effects and cause hypothermia [2], while a diethyl ether of L-glutamic acid shows neurotropic properties [3]. In this respect, special interest attaches to combinations of neurotropic amino acids (or oligopeptides) with N-1,2:3,4-di-О-isopropylideneαa-D-galactopyranosyluronic acid (DAGU). It was found that novel N-uronoyl derivatives of amino acids, such as N-(1,2:3,4-di-O-isopropylidene-αa-D-galactopyranuronoyl)-β-alanine (DAGU-Ala), DAGU-glycyl-D,L-glutamic acid (DAGU-GlyGlu) and DAGU-glycyl-glycine (DAGU-Gly-Gly), possess clearly pronounced neurotropic effects [4]. However, the mechanisms underlying such effects remain unstudied. This is why our work was aimed at obtaining the corresponding data.
METHODSWe recorded the activity of 118 neurons of the parietal ganglion (65 PPa1 ...