Cyclopropyl glycine and proline-containing preparation noopept evoke two types of membrane potential responses in synaptoneurosomes.

Proline, cyclo(Pro-Gly), and acyl-prolyl-containing dipeptide GVS-111 decreased synaptoneurosome membrane potential in a Ca2+-free medium. The efficiency of these preparations decreased in the following order: GVS>cyclo(Pro-Gly)>proline. Depolarization responses induced by endogenous nootropic agent cyclo(Pro-Gly) was dose-dependent and saturable; the threshold concentration of cyclo(Pro-Gly) was 10(-9) M. In a Ca2+-containing medium GVS and cyclo(Pro-Gly) induced both hyperpolarizing and depolarizing membrane responses of synaptoneurosomes. Possible mechanisms underlying changes in the membrane potential of synaptoneurosomes induced by nootropic agents are discussed. It was interesting whether modulation of electrogenesis can improve memory and potentiate the neuroprotective effect of the test nootropic agents.

Dipeptide analog of neurotensin active site prevents the development of experimental Parkinson's syndrome in mice.

Chronic administration of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) to C57BL/6 mice caused death of all animals within 7 days. Dipeptide analog of neurotensin active site injected with this neurotoxin protected the mice from death even after 2-week intoxication. When younger mice and lower dose of neurotoxin (25 mg/kg) were used, all animals survived, but after 2 weeks they developed parkinsonian syndrome with muscular rigidity, akinesia, decrease in motor and explorative activities. In mice treated with dipeptide analog of neurotensin active site these manifestations of oligokinesia caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine were less pronounced and the corresponding parameters approximated the control values. Possible mechanisms of neuroprotective action of neurotensin active site analog are discussed.

Changes in phospholipid composition of synaptic membranes in medulla oblongata and frontal lobes of the cerebral hemispheres in cats with hemorrhagic shock.

We studied phospholipid composition of brain synaptic membranes isolated from cats with severe hemorrhagic shock. Changes in the medulla oblongata were most pronounced and manifested in decreased content of phosphatidylcholine. Changes in the phospholipid composition of synaptic membranes in the frontal lobes included an increase in phosphatidylinositol content and reduced content of phosphatidylserine. Accumulation of phosphatidylethanolamine in synaptic membranes was found in both the medulla oblongata and frontal lobes. These data help to understand the mechanisms underlying exhaustion of compensatory reserves in brain cells during severe hemorrhagic shock.

[The effect of leucine enkephalin on the development of a convulsive afterdischarge in the sensorimotor cortex of rats]. / Vliianie leitsin-énkefalina na razvitie sudorozhnogo sledovogo razriada v sensomotornoi kore krys.

The application of leucin-enkephalin solution (LEU) (2 micrograms/2 microliters) on stimulated region of sensomotor cortex did not influence threshold of direct and transcallosal cortex responses (DR and TCR). On coupling of repeated electrostimulation train (RET) (duration of impulse--0.1 ms; duration of train--10 s; frequency--10/s) with application of LEU (after every odd train) the changes of DR and TCR in course of even trains and latency of afterdischarge appearance were such as in control ones. Simultaneously LEU effectively depressed short posttetanic potentiation of DR and TCR and potentiation of amplitude and duration AD, evoked by RET. It is suggested that LEU released from neurons in the course of RET does not participate in initiation of seizure in sensomotor cortex. A possible role of LEU in sensomotor cortex is limitation of intensity and duration of seizures and prevention of status epilepticus.

[The effect of a peptide-containing extract of the right hemispheric cortex on the recovery of conditioned reflex activity and on the level of neuromediators in the brain structures of rats after a unilateral frontal lobectomy]. / Vliianie peptidsoderzhashchego ékstrakta kory pravogo polushariia na vosstanovlenie uslovnoreflektornoi deiatel'nosti i uroven' neiromediatorov v strukturakh mozga krys posle odnostoronnei frontal'noi lobéktomii.

Experiments were conducted on 97 non-inbred [correction of unbred] male rats to study the effect of a peptide-containing extract of the cortex of the right hemisphere of donor rats, who underwent left lobectomy 9 days before the experiment, on restoration of conditioned reflexes of bilateral avoidance and level of neuromediators in the brain structures of recipient rats with a similar damage to the cerebral cortex. It is shown that the brain extract from the right hemisphere of operated on donors has a much higher effect on the restoration of reflexes. At the same time it was found that in left frontal lobectomy this extract produces a most manifest effect on monoamine metabolism in the structures of the right intact hemisphere. It is suggested that a directed effect may possibly be produced on the development of compensatory-restorative process in the central nervous system by endogenous substances of peptide origin which are isolated from brain structures actively contributing to the restoration of disturbed functions.

[Effects of peptide factors from right and left brain hemispheres of rats on amplitude-time characteristics of projective and interhemispheric evoked responses]. / Vliianie peptidnykh faktorov pravogo i levogo polusharii krys na amplitudno-vremennye kharakteristiki proektsionnykh i mezhpolusharnykh vyzvannykh otvetov.

Peptide extracts of the right and left hemispheres were applied to the projective (somatosensory and visual) and temporal associative regions of the left brain hemisphere in cats. In the zones of peptide application, evoked potentials (EP) in response to singular and coupled somatic, visual and transcallosal stimuli were registered. The data obtained showed that right and left peptide extracts had different effects on evoked potentials of the left hemisphere. Thus ipsilateral extract increased the amplitude of projective EP, decreased duration of their cycles and amplitude of transcallosal responses. Contralateral extract, on the contrary, activated interhemispheric inputs to brain cortex, suppressed thalamic inputs and increased multimodal properties of neurons. A differential approach to the problem of specific correction of pathological states of the right and left brain hemispheres is required. Right and left peptide extracts may be used in normalization of interhemispheric activity balance in compensatory-recovering processes.

[Effect of brain extracts from rats subjected to korazol kindling on generalized epileptic activity]. / Vliianie ékstraktov mozga krys, podvergshikhsia korazolovomu kindlingu, na generalizovannuiu épilepticheskuiu aktibnost'.

The pharmacological kindling was induced in rats by corazol repeated injections in subthreshold doses. The peptide-containing fraction was emitted from animal brains by the help of hot acetic acid on the stage of generalized clonic-tonic seizures development. Intraperitoneal injection of brain extracts of kindled rats significantly increased corazol and picrotoxin induced seizure severity in mice. The effect was removed by preliminary injection of naloxone or by preventive incubation of extracts with pronase. Intraventricular injection of extracts to intact rats increased the seizure severity which was provoked by corazol and in high doses induced in rats generalized seizure reactions.

[Action of cortical extracts of the left and right hemispheres on the recovery of conditioned reflex activity in rats after unilateral removal of the frontal cortex]. / Deistvie ékstraktov kory levogo i pravogo poluosharii na vosstanovlenie uslovno-reflektornoi deiatel'nosti krys posle odnostoronnego udaleniia lobnoi kory.

The recovery of active avoidance conditioned reflex (AACR) was investigated after unilateral frontal cortex extirpation. Intraperitoneal injection of extracts from left or right brain cortex (1 mg/kg) of healthy rats (LE or RE) stimulated AACR recovery in animals with lobectomy on the same side. If RE was extracted 9 days after left side brain extirpation, i.e. during the period of the development of compensatory processes, its effect on AACR recovery was stronger in left-operated animals, while in right-operated animals it remained unchanged.

[Asymmetric distribution of peptide regulators of muscle tonus and substance P in the spinal cord of rats with unilateral hyperactivity of the lumbar enlargement neurons]. / Asimmetriia raspredeleniia peptidnykh reguliatorov myshechnogo tonusa i substantsii P v spinnoi mozge krys s unilateral'noi giperaktivnost'iu neironov poiasnichnogo utolshcheniia.

The injection of tetanus toxin in m. gastrocnemius of the left or right hind limb of rats evokes ipsilateral hyperactivity of lumbar neurons in the spinal cord. In this case the lumbar enlargement extract after its intracisternal injection to healthy animals increases the duration of hind limb passive extension on the side where the donor neurons are hyperactive. The extract of the spinal cord of healthy rats was ineffective. Proteolysis of the extract with pronase or co-injection of opiate antagonist--naloxone--completely eliminated the lateralized changes in the muscular tone of the recipient. Substances that cause the unilateral changes in the muscular tone of the recipient are believed to be peptides. They are assumed to be involved in the functioning of endogenous opioid system. The level of substance P in the donor spinal cord was elevated bilaterally, but was higher in the hyperactive half of the spinal cord.

[45Ca2+ and 3H-GABA transport in nerve endings separated from the cerebral cortex of rats with hypoparathyroidism]. / Transport 45Ca2+ i 3H-GAMK v nervnykh okonchaniiakh, vydelennykh iz kory golovnogo mozga krys s gipoparatireozom.

Ca2+ blood serum level was reduced by 34.5% in rats with hypoparathyroidism (HPT) on the 7th-12th day after the damage of parathyroid glands. Synaptosomes isolated from the brain cortex of rats during this period accumulated in a normal medium more 45Ca2+ than synaptosomes from healthy animals. In potassium depolarization, control and experimental synaptosomes accumulated more 45Ca2+, however in HPT the increment in 45Ca2+ uptake in high potassium medium was less temperature-dependent. In normal medium 3H-GABA uptake and release by synaptosomes from the brain of rats with HPT slightly differed from those in the control. On the contrary, 3H-GABA release induced by synaptosome depolarization was depressed in HPT. It is suggested that nerve terminal excretory function disturbances contribute to increased excitability of the central nervous system in hypoparathyroidism.

[Effect of parathyroid hormone on the transport of 45Ca2+ and 3H-GABA in nerve endings isolated from the rat cerebral cortex]. / Vliianie paratireoidnogo gormona na transport 45Ca2+ i 3H-GAMK v nervnykh okonchaniiakh, vydelennykh iz kory golovnogo mozga krys.

Parathyroid hormone (PTH) (0.1-10 ng/ml) evokes a dose-dependent increase in 45Ca2+ accumulation in synaptosomes isolated from the rat brain cortex. In the presence of PTH the fast (I sec) potential-dependent 45Ca2+ uptake was less than in the control. PTH had no effect on 3H-GABA uptake by synaptosomes (P2 fraction). Synaptosomes preincubated in the presence of PTH in Ca2+-free medium and transferred into Ca2+-containing normal medium released more 3H-GABA than control synaptosomes. In this case depolarization-evoked 3H-GABA release was diminished.

[Peptidergic asymmetry of the rat spinal cord]. / Peptidergicheskaia asimmetriia spinnogo mozga krys.

Intracisternal administration of extractant-1M 90 degrees C acetic acid within 15 min into intact rats neutralizes the left and the right half of the lumbar part of the rat spine thus prolonging passive extension, while dorsal application causes the muscle tension of the back extremity. The effects are probably due to the peptidergic asymmetry of the rat spine.

[Mechanism of the suppression of the spinal pain syndrome by serotonin derivatives]. / Mekhanizm podavleniia spinal'nogo bolevogo sindroma proizvodnymi serotonina.

The ability of serotonin derivatives to stimulate cAMP accumulation in isolated nerve terminals and lumbar enlargement of the spinal cord of normal rats was compared. The effect of the compounds on the intensity of spinal pain syndrome was also assessed. It has been established that substitutes injected into NH2-group of serotonin in 5-OH position attenuate the ability to stimulate cAMP accumulation in synaptosomes, with the effect more pronounced with substitutes of larger volume. A certain correlation between the ability of serotonin derivatives to stimulate adenylate cyclase in vivo and in vitro, on the one hand, and their analgetic effect, on the other hand, is suggested.