The effects of corticotropin-releasing factor on anoxia-induced changes in evoked potentials in living slices of rat olfactory cortex.

Experiments were performed to address the dynamics of evoked focal potentials in slices of rat olfactory cortex during 10-min anoxia and subsequent reoxygenation. These experiments showed that perfusion with corticotropin-releasing factor (CRF)--corticoliberin--at concentrations of 1, 10, and 100 nM had no effect on changes in EPSP parameters before or during anoxia. However, CRF (10 and 100 nM) significantly aided recovery of the amplitude and slope of EPSP during reoxygenation. Application of the competitive NMDA receptor blocker APV (50 microM) during reoxygenation did not eliminate the protective effects of CRF on neuronal activity.

[Effect of corticotropin-releasing factor on anoxia-induced changes in evoked potentials in cultured tissue of the rat olfactory cortex]. / Vliianie kortikotropin-rilizing faktora na indutsirovannye anoksiei izmeneniia vyzvannykh potentsialov v perezhivaiushchikh srezakh oboniatel'noi kory mozga krys.

The experiments were performed on incubated slices of the rat rostal olfactory cortex. The slices were treated with various concentrations (10(-7) to 10(-9)) of corticotropin-releasing factor before (40 min), during, and after a 10-minute anoxic episode. The parallel control experiments were carried out without CRF. A 10-minute anoxia, both in control experiments and in perfusion with CRF, resulted in an approximately equal decrease of field excitatory postsynaptic potential's (fEPSP) amplitude. However, CRF at 10 nM and 100 nM concentrations protected the fEPSP amplitude. The selected NMDA receptor antagonists 2-amino-5-phosphonopentanoate (AP5) added in the perfusion medium after the anoxia, did not eliminate the neuroprotective effect of CRF.

[Effect of various concentrations of corticoliberin on long-term potentiation in slides of the rat olfactory cortex]. / Vliianie razlichnykh kontsentratsii kortikoliberina na dolgovremennuiu potetsiatsiiu srezov oboniatel'noi kory mozga krys.

Perfusion of the rat olfactory cortex slices with 1 mcM corticotropin-releasing factor (CRF) increased the rate of initiation of the posttetanic potentiation. The latter had a shorter supporting phase than in the control. With the perfusion, with 0.1 mcM the potentiation had a longer supporting phase than in the control.

Modulation by acute stress of chloride permeation across microdissected vestibular neurons membranes: different results in two rabbit strains and CRF involvement.

Free hand isolation of adult rabbit vestibular Deiters' neurons and dissection of their single membranes allows the study of their ionic permeability characteristics in a microchambers device. In the case of hare-like rabbits, the dissection of such membranes presents evidence of a high basal permeation of labelled chloride, possibly related to mechanical disturbance of the plasma membrane-related cytoskeleton and activation of chloride channels. This did not apply to the laboratory strain of white New Zealand rabbits. However, membranes from hare-like rabbits which were stressed by being rotated on a platform before the experiment, behaved like those from the New Zealand strain. Vice versa, habituation to handling day after day of New Zealand rabbits resulted in a chloride permeation equal to that of unstressed hare-like rabbits. We propose that the stressful conditions result in the release of neurochemical messages to the vestibular Deiters' cells which influence their electrophysiological behavior. The corticotropin releasing factor (CRF), a stress-related peptide present in the climbing fibers, actually blocks the basal chloride permeation across the Deiters' membranes and this effect is partially reversed by its receptor antagonist, alpha-helical CRF [9-41].

Morphine decreases the voltage sensitivity of slow sodium channels.

Cell membrane recordings were made in conditions of voltage clamping with tight attachment of the microelectrode-patch clamping--to study the effects of morphine on tetrodotoxin-resistant (TTXr) sodium channels in rat spinal ganglion neurons in culture. The effects of a number of biologically active substances which regulate the receptor-mediated actions of morphine were studied. The effects of morphine were found to involve a chain of sequential reactions leading to decreases in the transfer of effective charge (Zeff) by the activatory gate system of TTXr sodium channels, depending on the concentration of agonist in the extracellular solution. A value of 8 nM was obtained for KD. with a Hill coefficient of X = 0.5. Non-specific antagonists of opioid receptors blocked the actions of morphine; these included ouabain at a concentration of 100 microM. An inhibitor, and activator, and a blocker of G-proteins had no effect on the effective charge. These data provide evidence that morphine decreases the voltage sensitivity of TTXr sodium channels.

[Morphine decreases the voltage sensitivity of the slow sodium channels]. / Morfine umen'shaet chuvstvitel'nost' k potentsialu medlennykh natrievykh kanalov.

Morphine was shown to decrease in a dose-dependent manner the effective charge transfer in tetrodotoxin-resistant (TTXr) sodium channel activation system in short-term cultured dorsal root ganglion cells. Morphine seems to interact with opioid receptors because of total block of the binding by naloxone and naltrexone. Neither activating, nor inhibiting G-protein agents exerted any effect on this process. The morphine signal was blocked by extracellular application of 2 x 10(-4) M ouabain. The findings suggest existence of sodium signalling pathway involving receptors, Na+, K(+)-ATPase and the TTXr sodium channels.

Role of G-proteins and second messenger systems in the plasticity of a defensive reflex in the common snail.

Enzymatic methods were used to demonstrate an increase in the activity of G-proteins and protein kinase A in the brain of the common snail at early stages of learning. There were no differences in the activity of G-proteins in the brain between young (unable to learn) and adult snails. Snail brain protein kinase C activity was unchanged compared to controls 20-40 minutes after the end of the training procedure. It is concluded that cAMP-dependent phosphorylation and cAMP-dependent activation of early gene expression have active roles in learning in the snail. The question of the role of additional intracellular regulatory systems in learning in the snail is discussed.

Number of correlates of membrane metabolism and long-term potentiation in rat brain slices.

Long-term potentiation was elicited in living slices of rat olfactory cortex by stimulation of the lateral olfactory tract. A group of interdependent parameters of membrane metabolism was studied, i.e., the kinetics of 45Ca metabolism, lipid peroxidation, and antioxidant defense; cytochemical measurements were made of Na+, K(+)-ATPase activity in neurons and glial cells; the functional (GTPase) activity of G-proteins was also studied. All parameters were compared with the bioelectrical activity of slices at three time points after tetanization, i.e., 3-5, 15, and 30 min. In most cases, regular phasic changes in metabolic parameters occurred, and their functional significance is discussed.

Na+,K(+)-ATPase activity in neurons and glial cells of the olfactory cortex of the rat brain during the development of long-term potentiation.

Na+,K(+)-ATPase and Mg(2+)-ATPase activities were studied in neurons and glial cells of the olfactory cortex of the rat by quantitative cytophotometry in conditions of long-term potentiation (LTP), and significant changes in direction and extent were found. Na+,K(+)-ATPase activity decreased in neurons in the first 15 min after LTP, with subsequent elevation by 30 min. Mg(2+)-ATPase activity remained unchanged in these conditions. Glial cells showed significant increases in Na+,K(+)-ATPase activity in the initial period after LTP, with return to control by 30 min. Again, there were no significant changes in Mg(2+)-ATPase activity. The formation and persistence of LTP in neurons and glial cells was accompanied by significant changes in Na+,K(+)-ATPase activity, which were reciprocal in nature.

[The role of G-proteins and second messenger systems in the plasticity of the avoidance reflex in the snail]. / Rol' G-belkov i sistem vtorichnykh posrednikov v plastichnosti oboronitel'nogo refleksa u vinogradnoi ulitki.

An increase in the activity of G-proteins and protein kinase A was shown in the brain of Helix at the early stages of learning. The protein kinase C activity did not differ from the baseline in 20-40 min after training. There was no difference between the brain G-protein activities in the young (unable to learn) and adult snails. A conclusion is drawn that the system of cAMP-dependent phosphorylation and cAMP-dependent activation of the early genes actively participate in learning of Helix. The participation of additional systems of intracellular regulation in learning is discussed.

[Correlates of membrane metabolism and long-term potentiation in slices of rat cerebral cortex]. / Nekotorye korreliaty membrannogo metabolizma i dolgovremennoi potentsiatsii v srezakh kory mozga krys.

A group of interrelated parameters of the membrane metabolism was studied during stimulation of the lateral olfactory tract in the rat brain slices of olfactory cortex. All the parameters were studied in respect to electrical activity of the slices in three temporal points after the tetanisation: 3-5, 15, and 30 min. Regular phasic alterations of the metabolism parameters occurred in most of the cases. Their functional significance is discussed.

[Na(+),K(+)-ATPase activity in the neurons and glial cells of the olfactory cortex of the rat brain in the dynamic development of long-term potentiation]. / Aktivnost' Na(+),K(+)-ATFazy v neironakh i glial'nykh kletkakh oboniatel'noi kory golovnogo mozga krys v dinamike razvitiia dolgovremennoi potentsiatsii.

The initial stationary phase of the LTP was followed by a decrease in the Na(+),K(+)-ATPase activity of neurons and an augmentation of enzyme activity in the glial cells. Decay of the LTP tends to normalize the above types of activity.

[Effect of polymer modification of insulin on its enzymatic hydrolysis and conformation properties]. / Vliianie polimernoi modifikatsii insulina na ego fermentativnyi gidroliz i konformatsionnye svoistva.

AI, B29 insulin polymeric derivatives in which the polymeric chains (N-polyvinylimidazole, N-polyvinylpyrrolydone and polyacrylic acid) are bonded to the insulin molecule at one point were synthesized. The hydrolysis of the modified insulin by trypsin is dependent to a great extent on the chemical nature of the modifying polymer and is virtually independent of its molecular weight up to 20 kD. The effect of the modifying polymer manifests itself mainly in a change of the Michaelis constant. Investigation of the conformational properties of the insulin derivatives by the method of optical rotatory dispersion revealed that insulin modification by polymers caused a decrease of the amino acid content in the alpha-helical sequence from 41 to 33-30%. The chemical nature of the modifying polymer and its molecular weight have a profound effect on the conformational stability of the residual spatial structure of the modified insulin in alkaline media.

[Effect of insulin and its polymeric analogs on learning and memory processes in the rabbit]. / Vliianie insulina i ego polimernykh analogov na protsessy obucheniia i pamiati u krolikov.

The effect of insulin and its seven synthetic derivatives on spontaneous bioelectrical activity of the cerebral cortex of rabbits was described in the paper. The influence of these substances on consolidation of long-term memory of white rats was shown at normal state and during experimental neurosis. Insulin was supposed to influence the higher nervous activity not only through glucose metabolism but also by means of increase of permeability of biological membranes for amino acids.

[Intramolecular modification of azisobutyrylinsulin and the use of the modified hormone for the synthesis of polymeric derivatives]. / Sintez vnutrimolekuliarno sshitogo azoizobutirilinsulina i poluchenie na ego osnove polimernykh proizvodnykh gormona.

An intramolecular modification of insulin at the alpha-amino group of glycine (A1) and the epsilon-amino group of lysine (B29) was carried out. The modification resulted in a slight alteration of the insulin secondary structure; the modified hormone possessed a biological activity which was practically identical to that of the natural hormone. Therefore the modified insulin can be used as a high molecular weight physiologically active radical inducer for the synthesis of (A1-B29) polyvinylimidazole derivatives. The molecular weight of the covalently linked polymer can be variable. It was shown that the increase in the amount of modifying polymer in the conjugate results in stabilization of the insulin secondary structure concomitant with a decrease of the biological activity and, moreover, of the immunoresponsiveness of the hormone.

[Synthesis and properties of insulin modified on phenylalanine of chain B]. / Sintez i izuchenie insulina modifitsirovannogo po fenilalaninu tsepi B.

Lysyl and tetralysyl derivatives of insulin on phenylalanine of chain B were synthesized. The effects of modifications on the spatial structure and biological properties of the hormone were studied. It was found that an increase in the length of the modifier leads to a distortion of the hormone spatial structure resulting in a decrease of its biological activity.