[The effect of MPTP on the neuronal uptake of monoamines]. / Vliianie MFTP na neironal'nyi zakhvat monoaminov.

The results of kinetic analysis of synaptosomal uptake of dopamine, noradrenaline, adrenaline and serotonin showed the presence of their own carrier systems with high or low affinity for each monoamine. The low affinity system of the uptake of monoamines by nerve endings differs from extraneuronal one by higher affinity. MPTP noncompetitively inhibits the system of highly effective uptake of the studied monoamines by nerve endings, competitively inhibiting synaptosomal uptake with low affinity of noradrenaline, adrenaline and noncompetitively serotonin and dopamine. The constant values of inhibition showed that MPTP most strongly blocks the system of synaptosomal uptake of low affinity serotonin and approximately 2-times weaker affects its system of high affinity. Carrier systems of high affinity of dopamine, adrenaline and noradrenaline block MPTP 150-500 times weaker than that of serotonin, and as for low affinity--in 2000-4000 times. It may be supposed that synaptosomal uptake of low affinity serotonin is most perceptible to the effect of MPTP and is of a particular importance in the development of Parkinson's disease symptoms.

[Effects of amiridin and tacrine, drugs effective in Alzheimer's disease, on synaptosomal uptake of neuromediators]. / Vliianie amiridina i takrina--preparatov, éffektivnykh pri bolezni Al'tsgeimera, na sinaptosomal'nyi zakhvat neiromediatorov.

The study of the drugs effective in the treatment of cognitive deficits and memory loss associated with senile dementia of the Alzheimer's type--tacrine and amiridin, acetylcholinesterase inhibitor physostigmine and nootrop piracetam on uptake of 3H-serotonin (3H-5-HT), 3H-adrenaline (3H-AD), 3H-noradrenaline (3H-HA), 2H-dopamine (3H-DA), 3H-gamma-aminobutyric acid (3H-GABA), 3H-glutamic acid (3H-GLU), 3H-aspartic acid (3H-ASP) and 3H-glycine (3H-GLI) showed that tacrine and amiridin (5 x 10(-5) M) statistically significantly (P less than 0.05) inhibited the uptake of 3H-DA and 3H-5-HT. Physostigmine at concentration 5 x 10(-4) M statistically significantly (P less than 0.05) inhibited uptake of 3H-5-HT only. Piracetam at concentration range 1-5 x 10(-3) M had no effect on uptake of all investigated neurotransmitters. The above finding suggest that the uptake of neurotransmitter in nerve terminals is not the main target of amiridin and tacrine.

[Uptake of adrenaline by rat brain synaptosomes. Effects of several psychotropic drugs]. / Zakhvat adrenalina sinaptosomami mozga krys. Vliianie nekotorykh psikhotropnykh veshchestv.

Comparative study of the uptake of 3H-epinephrine (3H-EN) and 3H-norepinephrine (3H-NE) into rat brain crude synaptosomes and effect of psychotropic drugs of different classes on this process showed that isolated nerve terminals had their own transport system for EN. The crude synaptosomal fraction had two transport system's for EN; high-specific active uptake with high affinity (KM = 3.7 + 0.21 microM) and low-affinity uptake (KM2 = 98.0 + 47.5 microM). En accumulation was saturable, stereo-specific and inhibited by ouabain (3 X 10(-3) M), protoveratrine A and B (10(-4) M), NaN3 (2 X 10(-3) M), 2,4-dinitrophenol (2 X 10(-3) M), p-chloromercuribenzoate (10(-4) M). Actinomycin D had no effect on the uptake of 3H-EN. 3H-HE was accumulated by two uptake system: 1-high affinity uptake system with KM values of 0.49 + 0.13 microM, 2-low affinity uptake system with KM values of 21.1 + 7.71 microM. Amphetamine, mesocarb, chlorpromazine, fluphenazine and haloperidol were equally effective inhibitors of 3H-EN and 2H-HE uptake. Imipramine, phenazepam, diazepam and carbamazepine (5 X 10(-5) M) had no effect on the uptake of 3H-NE. Imipramine, zimelidine, norzimelidine and viloxazine (5 X 10(-5) M) were more potent inhibitors of the 3H-EN uptake than that of 3H-NE.

[The effect of antimigraine preparations on serotonin transport in the brain synaptosomes of rats]. / Vliianie protivomigrenevykh preparatov na transport serotonina v sinaptosomakh mozga krys.

Methisergide and nicergoline act as competitive inhibitors whereas tolfenamic acid as a non-competitive inhibitor of 3H-serotonin accumulation which occurs with the involvement of the high-affinity system of serotonin uptake by the rat brain synaptosomes. Methisergide, nicergoline and tolfenamic acid at concentrations ranging close to Ki value were found to enhance the basal and K(+)-induced release of 3H-serotonin from the rat brain synaptosomes. The findings obtained indicate the ability of the drugs to disturb serotonin transport. In addition, the drugs are likely to exert the depleting effect on serotonin stores in serotoninergic neurons. Picamilon failed to affect either the uptake or the release of serotonin from the rat brain synaptosomes.

[Functional state of blood platelets in arterial hypertension and the changes in serotonin-containing cellular granules]. / Funktsiona'lnoe sostoianie krovianykh plastinok pri arteria'lnoi gipertonii i izmeneniia serotoninsoderzhashchikh granul kletok.

The study was undertaken to examine the status of the granular apparatus and platelet aggregability in 9 healthy donors and 18 patients with arterial hypertension (AH), including 14 with essential hypertension (EH) and 4 with symptomatic forms of AH. Among the patients, a group of 8 EH patients was singled out, who had, compared with normal, reduced relative volumes of electron dense platelet granules (from 17.9 +/- 2.0 to 5.3 +/- 0.6%). The group also showed lower platelet serotonin levels (from 67.3 +/- 5.3 to 17.6 +/- 3.7 ng per 10(8) cells; p less than 0.001) and a 2-fold decrease in the transport factor of acridine orange across the cytoplasmic and granular membranes as compared to normal. A positive correlation was established between the amounts of cellular serotonin and the relative volume of platelet granules (r = 0.850; p less than 0.001).

[Changes in the balance of biogenic monoamines and their metabolites in the organs of rats with oxygen-induced epilepsy]. / Izmenenie balansa biogennykh monoaminov i ikh metabolitov v organakh krys pri kislorodnoi épilepsii.

The content of some biogenic monoamines and their metabolites in rat brain and heart in different periods of oxygen epilepsia was studied using high performance liquid chromatography with electrochemical detection. It was shown that already at the 5th minute of exposure to oxygen adrenaline, DOPA and some noradrenaline metabolites disappeared in the brain and noradrenaline level reduced. At this period in rat heart the reduction of catecholamine content was the most distinct and serotonin level was unchanged. At the beginning of convulsive period the modifications of biogenic amines content were nonparallel in brain regions: in the heart the reduction of catecholamine level went on, especially in right ventricle. In the terminal phase of oxygen epilepsia brain biogenic amines increased, however, not up to normal meaning, heart catecholamines at this period were at the same level as at the beginning of the convulsive period.

[Determination of monoamines and 10 of their metabolites in the brain and heart of the rat by high-pressure liquid chromatography with electrochemical detection]. / Opredelenie monoaminov i 10 ikh metabolitov v mozge i serdtse krysy metodom zhidkostnoi khromatografii vysokogo davleniia s élektrokhimicheskoi detektsiei.

The adequate parameters for simultaneous determination of more than 10 monoamines, their precursors and metabolites (noradrenaline, 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydrooxyphenylglycol++, vanylylmandelic acid, normetanephrine, adrenaline, metanephrine, dopamine, 3-methoxytytramine, 3,4-dihydroxphenylacetic acid, 3,4-dihydroxyphenylalanine, 5-hydroxytryptophane, 5-hydroxyindolacetic acid) by liquid chromatography with electro-chemical detection were suggested for the rat brain and heart. The influence of reserpine, iproniazid, and imipramine on the content of the changes of monoamines and their metabolite levels in the rat brain and heart were also investigated.

[Characteristics of the effect of psychotropic preparations on the synaptosomal uptake of monoamines]. / Osobennosti vliianiia psikhotropnykh preparatov na sinaptosomal'nyi zakhvat monoaminov.

The authors investigated the ability of psychotropic drugs of different classes (psychostimulants, antidepressants and tranquilizers) to inhibit the reverse synaptosomal uptake of monoamine neurotransmitters in the rat brain. The psychostimulants amphetamine and cocaine (50 microM) powerfully suppressed noradrenaline, dopamine and serotonin transport without influencing GABA uptake. Phenazepam (50 microM) negligibly decreased the reverse synaptosomal uptake chiefly of noradrenaline. Studies of the antidepressants evidenced that inkazan is a highly selective inhibitor of the reverse uptake of serotonin, whereas other antidepressants such as zimelidine, imipramine and norzimelidine were discovered to inhibit the uptake of serotonin to a larger extent than that of other transmitters. The antidepressants pyrazidol and viloxazine turned out to be non-selective inhibitors of the transport of all monoamines tested. Iproniazide and moclobamide appeared inactive as regards the reverse uptake of monoamine neurotransmitters.

[Action of neurotropic substances on gamma-aminobutyric acid release from brain synaptosomes during K+ depolarization]. / Deistvie neirotropnykh veshchestv na vysvobozhdenie gamma-aminomaslianoi kisloty iz sinaptosom golovnogo mozga na fone K+-depoliarizatsii.

The effects of aminazine (0.25 mM), phthoracyzine (0.5 mM), trifluperidole (0.5 mM) and imipramine (0.5 mM) on GABA release from rat brain synaptosomes depolarized with K+ (50 mM) were investigated. Incubation of synaptosomes with aminazine led to a 2-fold and that with phthoracyzine, trifluperidole and imipramine to a 1.5-fold increase in GABA release from synaptosomes as compared with its basic level. The raising of K+ in the incubation medium to 50 mM brought about a 2-fold augmentation of GABA release. Exposure of synaptosomes to drugs and a higher K+ concentration at a time did not change GABA release as compared to its basic level. Introduction into the incubation medium of the Ga-ionophore A23187 together with 50 mM K+ and trifluperidole or with K+ and imipramine led to the same increase in GABA release from synaptosomes as that produced by the psychotropic drugs as regards native synaptosomes. It is assumed that the lack of the influence of the psychotropic drugs under study of GABA release from synaptosomes depolarized with K+ is caused by blockade of synaptic membrane conductibility for Ca2+.

[Mechanism of the inhibiting effect of atypical antidepressants and psychostimulants on the synaptosomal uptake of monoamines]. / Mekhanizm ingibiruiushchego vliianiia atipichnykh antidepressantov i psikhostimuliatorov na sinaptosomal'nyi zakhvat monoaminov.

The effects of viloxazine and zimelidine on reverse monoamine neurotransmitter uptake by crude synaptosomal fraction of the rat brain were studied and compared to those of imipramine, amphetamine and cocaine. Imipramine noncompetitively inhibited the uptake of all the monoamines under study, with a greater specificity as regards serotonin. Viloxazine and zimelidine strongly inhibited the transport of noradrenaline, dopamine and serotonine, the transport of the latter being inhibited to a greater degree. Kinetic analysis showed the active centers of noradrenaline and dopamine carriers to be very much alike, those of catecholamine and serotonin carriers to be less alike. The data obtained made it possible to describe (at least partly) the structure of the active centers of monoamine carriers and to specify the action modes of antidepressants and psychostimulants.

[Effect of different classes of psychotropic substances on 14C-glutamate uptake by crude synaptosomal fractions in the rat brain]. / Vliianie psikhotropnykh veshchestv raznykn klassov na zakhvat 14C-glutamata gruboi sinaptosomal'noi fraktsiei mozga krys.

Effects of different psychotropic drugs on the reverse uptake of glutamate by rat brain synaptosomes were investigated. The KM values for glutamate transport by high affinity and low affinity systems were calculated (30 and 300 microM, respectively). It is shown that neuroleptics, antidepressants, tranquilizers, psychostimulants, and narcotic analgesics at a concentration of 50 microM had no influence on the high affinity glutamate uptake. Meanwhile neuroleptics and tricyclic antidepressants at a concentration of 500 microM partly inhibited this process. The anticonvulsant diphenylhydantoin at a concentration of 500 microM stimulated synaptosomal uptake of glutamate. It is concluded that there is no correlation between the effects of psychotropic drugs on glutamate uptake and their specific action on the central nervous system.

[Atypical antidepressants: effect on synaptosomal uptake of serotonin and GABA]. / Atipichnye antidepressanty: vliianie na sinaptosomal'nyi zakhvat serotonina i GAMK.

Effect of the antidepressants of different chemical groups--imipramine, desmethylimipramine, chlorimipramine, befuralin, trazodon, pyrazidol, inkasan and azaphen--on the uptake of 3H-serotonin and 3H-GABA by the crude synaptosomal fraction of the rat brain was studied. The Cm values for the uptake of serotonin and GABA were 0.195 and 30 micro M, respectively. Inkasan and azaphen were the most potent inhibitors of the 3H-serotonin uptake (65-70% inhibition at a concentration of 50 micro M. Azaphen and chlorimipramine were the only ones to inhibit the uptake of 3H-GABA at a concentration of 50 micro M. The majority of the antidepressants studied inhibited the GABA uptake only at high concentrations.

[Effect of beta-phenylethylamine on synaptosomal and glial transport of labeled neuromediators]. / Vliianie beta-fenilétilamina na sinaptosomal'nyi i glial'nyi transport mechenykh neiromediatorov.

The effect of beta-phenylethylamine (beta-PEA) on the accumulation of 14C-serotonin, 14C-glutamate and 3H-gamma-aminobutyric acid (3H-GABA) by synaptosomes of the caudate nucleus and cerebral cortex of rats and rabbits was studied for the first time. beta-PEA inhibits 14C-serotonin influx and exerts no material effect on 14C-glutamate and 3H-GABA uptake. beta-PEA inhibits the synaptosomal and glinal accumulation approximately to the same extent. The data obtained are in good agreement with the concepts of the regulatory role of beta-PEA in the transport of biogenic monoamines in the nerve ending membranes. A similarity of the inhibitory effects of beta-PEA to those of amphetamine is suggested.

[Effect of psychotropic substances and narcotic analgesics on 14C-noradrenaline uptake by rat cerebral cortex synaptosomes]. / Vliianie psikhotropnykh veshchestv i narkoticheskikh anal'getikov na zakhvat noradrenalina-14C sinaptosomami kory mozga krys.

The effect of different groups of neurotropic substances was studied on labeled noradrenaline and gamma-aminobutyric acid (GABA) uptake by synaptosomes of the rat brain cortex. It has been shown that each group of the test compounds is characterized by specific qualitative and quantitative features of the action on the above processes. Thus, psychostimulants actively inhibit noradrenaline uptake without changing GABA uptake. On the contrary, neuroleptics exert a pronounced inhibitory effect on GABA uptake and insignificantly inhibit noradrenaline accumulation. Antidepressants are very potent while narcotic analgesic drugs are less potent inhibitors of the accumulation of both neuromediators. Morphine and nalorphine have no effect on these processes.

[Inhibition of serotonin uptake in synaptosomes and glia cells by some pharmacological substances]. / Ugnetenie nekotorymi farmakologicheskimi Veshchestvami zakhvata serotonina sinaptosomami i kletkami glii.

The uptake of serotonin -14 C by glial cells and synaptosomes of the rabbit brain cortex was studied. The Km value of the uptake of serotonin -14 C proved to be equal (0.83 + 0.02 microM) both for synaptosomes and glial cells. Synaptosomes of the rabbit brain cortex take up serotonin -14 C twice as fast as glial cells (uptake rates were compared from protein). Among psychotropic drugs studied the tricyclic antidepressant imipramine and psychostimulant cocaine turned out the most active inhibitors of both synaptosomal and glial uptake of serotonin -14 C. The drugs in 50 microM concentration inhibit the uptake of serotonin -14 C in synaptosomes and glial cells by 90 and 75-80%, respectively.

[Effect of psychotropic substances on dopamine uptake by synaptosomes and glial cells]. / Vliianie psikhotropnykh veshchestv na zakhvat dofamina sinaptosomami i glial'mymi kletkami.

Dophamine-H3 uptake by synaptosomes and glial cells of the cerebral cortex in rabbits and by the synaptosomes of the cerebral cortex in rats was studied. KM value of the dophamine-H3 uptake was found to be the same (0.075 +/- +/- 0.01 micrometer) in case of synaptosomes and glial cells. The rate of dophamine-H3 uptake by the rabbit cerebral cortex synaptosomes was twice that of the gial cells (as compared by protein). Among the psychotropic agents studied the most active symaptosome uptake inhibitors were phenamine and cocaine; they were less active in respect to glial uptake. Both types of uptake were inhibited by neuroleptics and antidepressants to the same degree. Results of this work conformed to the view on the participation of the strial dophaminergic link in the action mechanism of psychostimulants.

[Effect of neuroleptics on spontaneous and evoked noradrenaline release from brain nerve endings of rats]. / Vliianie neiroleptikov na spontannoe i vyzvannoe vysvobozhdenie noradrenalina iz nervnykh okonchanii mozga krysy.

Spectrofluorometric determination of the noradrenaline content in the non-purified fraction of the rat's brain stem synaptosomes and radioisotope method resulted in finding that carbidine is capable to release noradrenaline from the nerve endings. Azabutyron, droperidol and fluphenazine had no noticeable effect on this process. The release of noradrenaline with carbidine depends upon the presence of Ca2+ ions in the medium. This neuroleptic is also capable of intensifying the release of the mediator provoked by the potassium depolarization of the nerve endings.

[Tryptophan uptake by glia and synaptosomes of rabbit cerebral cortex]. / Zakhvat triptofana kletkami glii i sinaptosomami kory golovnogo mozga krolika.

The authors studied the engulfment of L-tryptophane-14C by gliacytes and synaptosomes of the rabbit cerebral cortex. The system of engulfment of the gliacytes was characterized by a high affinity to tryptophane (Km = 0.8 micrometer). Engulfment of tryptophane by synaptosomes had a lower affinity (Km = 50 micrometer). Psychotropic substances--chlorpromazine and imipramine produced an inhibitory influence on glial engulfment. The leading role of gliacytes in the trophic provision of the neurons and the normal course of neurodynamic processes is confirmed.

[Uptake of gamma-aminobutyric acid by 3H-glial cells and synaptosomes of rat cerebral cortex under the influence of psychotropic substances]. / Zakhvat gamma-aminomaslianoi kisloty 3H-glial'nymi kletkami i sinaptosomami kory mozga krys pri deistvii psikhotorpnykh veshchestv.

Chlorpromazine was shown to inhibit non-competitively the 3H-GABA uptake both by the glial cells and synaptosomes; synaptosomal uptake was more sensitive to the inhibitor. Only the low-affinity GABA uptake in the glial cells was competitively inhibited by beta-alanine. On the whole, there was a correlation between the inhibition of GABA uptake by psychotropic drugs in the glial cells and in the synaptosomes. It is assumed that there existed two different systems of GABA uptake (of high and low affinity) in the nerve endings and glial cells.