Localization of lysine residue in histone H3 forming the thymine-lysine cross-link after UV-irradiation of deoxyribonucleoprotein

A thymine-modified derivative of histone H3 formed as a result of thermal treatment of UV-irradiated (lambda = 254 nm) solution of deoxyribonucleoprotein from calf thymus at low ionic strength was isolated. The peptides obtained by tryptic hydrolysis of modified histone H3 were separated by high pressure liquid chromatography. The amino acid sequence of the peptide containing a lysine residue with covalently linked thymine was determined by the Edman method. It was found that Lys localized at the N-terminus of the histone H3 molecule interacts with DNA within the composition of the deoxyribonucleoprotein.     

Multiple mechanisms underlying nootropic drug-induced enhancement of neuronal responses mediated by activation of glutamate NMDA-type receptors

Nootropic drugs of various chemical structure (pyracetam, dimethylaminoethanol, ethymisol, and ambocarb) possessing antiamnesic activity were found to increase depolarization evoked by L-aspartate and the EPSP late components evoked by dorsal roots stimulation (DR-EPSP). Experiments were performed on motoneurons of the lumbar region of isolated frog spinal cord superfused with Mg²⁺-free saline. When ionic channels of NMDA-glutamate receptors were blocked with ketamine and Mg²⁺, the nootropic substances did not affect DR-EPSP and motoneuronal depolarization evoked by L-glutamate. Butamid, a protein kinase A inhibitor, blocked the ethymisol and pyracetam effects, whereas polymixin B, a protein kinase C inhibitor, blocked the ambocarb effect. Trifluoroperazine, a calmodulin inhibitor, blocked the effect of dimethylaminoethanol. Proline inhibited only the pyracetam effect. These results indicate that the NMDA-potentiating activity of the above nootropic drugs may be based on both intracellular phosphorylation of NMDA receptor-channel complexes, as mediated by protein kinases, and allosteric enhancement of affinities of these complexes to excitatory amino acids.Neirofiziologiya/Neurophysiology, Vol. 25, No. 3, pp. 179–184, May–June, 1993.     

Effect of serotonin on smooth muscle]

Serotonin caused contracion of the smooth muscles of the deferent duct and of the strip of rat stomach, acting upon the D-serotonin receptors. Only a small portion of its contractile effect (about 10--14%) was caused by the release of endogenous catecholamines. The action of serotonin on the strip of the rat stomach was accompanied by an increase of its entrance into the cells of Ca45 and Na22 isotopes. The concentration turn of the concentration-effect curve of serotonin on the stomach strip was connected with the accumulation of sodium ions in the cells.     

Participation of neuronal NO-synthase in regulation of hypothalamus vasopressinergic neurons of rat pups at early stages of postnatal ontogeny

To reveal character of interaction of catecholamines (CA) and NO in regulation of development and of the functional state of vasopressinergic (VP-ergic) neurons of supraoptic (SON) and paraventricular (PVN) nuclei, the female rats were injected intraperitoneally with the inhibitor of CA synthesis α-methyl-p-tyrosine, daily, from the 13th to the 20th days of pregnancy. Rat pups born by the females administered with saline at the same period of pregnancy as well as intact pups and adult rats were used as control. Expression of neuronal NO-synthase (nNOS) in neurons of SON and PVN of rat pups at early stages of postnatal development was found to be significantly higher than the definitive level, which allows suggesting participation of NO in development of hypothalamic VP-ergic neurons. The revealed differences of periods of the maximal nNOS expression in the SON and PVN neurons have permitted suggesting development of SON to be completed earlier than that of PVN. The pups exposed to stress at the last third of embryonic development had a long-lasting effect on the state of VP-ergic neurons of the pups after birth. The nNOS expression in neurons does not change, which suggests that NO is not involved in regulation of VP-ergic neurons after exposure to stress at early stages of ontogenesis. A decrease of CA level in the brain at the last third of embryogenesis led to a long preserved decrease of the functional activity of VP-ergic neurons. The nNOS expression in VP-ergic neurons of SON and PVN rose substantially under effect of a compensatory enhancement of tyrosine hydroxylase (TH) expression in neurons of SON and of an increase of the level of CA-ergic innervation of PVN. Thus, we have shown that a decrease of CA level in the embryonic brain leads to an increase of nNOS expression of hypothalamic VP-ergic neurons of rat pups after birth and that the character of NO action on function of VP-ergic neurons does not differ from that of adult animals as soon as at early stages of ontogenesis.     

Polymethylene derivatives of nucleic bases with ω-functional groups: VI. [8-(2-oxocyclohexyl)-9-oxooctyl]pyrimidines as potential inhibitors of pyrimidine phosphorylases

New polymethylene derivatives of nucleic bases with β-diketo function in ω-position were prepared by alkylation of uracil, thymine, and cytosine. Their physicochemical properties and effect on the E. coli uridine and thimidine phosphorylases were studied.     

Characteristics of GABA-potentiating effect of harman

Experiments on an isolated spinal cord of rats aged 9-15 days have shown that harmane (10(-7)-10(-5) M) enhances GABA-induced (1.10(-4) M) depolarization of primary afferents and hyperpolarization of motoneurones. The GABA-potentiating action of harmane on primary afferents is depicted by a bell-shaped curve with a maximum at 10(-5) M. The action is more pronounced the higher the concentration of chlorine ions in the medium. Harmane (10(-6)-10(-4) M) enhances spontaneous neuronal activity and evoked synaptic potentials (mono- and polysynaptic potentials of the ventral and dorsal roots) at the concentrations at which it exerts a direct depolarizing action on motoneurones and primary afferents. At higher concentrations the stimulant activity of harmane (10(-5)-10(-4) M) counteracts its GABA-potentiating effects.     

Monoaminergic mechanisms of the amygdaloid complex actualizing conditioned reflexes of different biological modality]

Microinjection of dopamine and serotonin into the dorso-medial portions of the amygdalic complex of rats increased the latent period of conditioned defense and motor food reactions, spontaneous motor activity, the number of jerks and the value of the conditioned food reflex. Noradrenaline failed to influence the recorded indices of the conditioned food-procuring reflex, but facilitated the conditioned reaction of avoidance, significantly shortening its latent time. The results obtained pointed to the specificity of the neurochemical mechanisms realizing at the level of the amygdalic complex conditioned reflexes of various biological modality in rats.