Analysis of the effect of morphine and trimeperidine on the uptake and liberation of noradrenalin by myocardial tissue

The effect of morphine and trimeperidine on the concentration, uptake, and liberation of noradrenalin (NA) in the rat myocardium was investigated. Trimeperidine lowers the NA level in the myocardium. Morphine does not affect the liberation of NA-¹⁴C from the isolated perfused heart, whereas trimeperidine significantly increases it, affecting both the slow and the rapid release of the mediator. Trimeperidine does not affect the uptake of NA-¹⁴C by the perfused heart but morphine significantly lowers it. Competition between morphine and NA is characterized by an incomplete inhibition effect: Morphine and NA mutually affect the affinity of each other for the receptor and their interaction depends on their relative concentrations.Laboratory of Pharmacology of the Cardiovascular System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 11, pp. 1345–1347, November, 1976.     

Effect of psychotropic drugs on synaptosomal uptake of H3-γ-aminobutyric acid and on Na,K-ATPase activity

Neurotropic drugs belonging to various groups (fluphenazine, nonachlazine, trifluperidol fluacizine, imipramine, diazepam, apomorphine fetanyl, diphenylhydantoin) in experiments in vitro showed an inhibitory effect on active transport of -aminobutyric acid (GABA) by synaptosomes of the rat cerebral cortex. In most cases a parallel decrease in the activity of synaptosomal Na,K-ATPase was observed. Substances not changing GABA uptake as a rule had no effect on the activity of the enzyme (carbidine and morphine). Some substances inhibiting Na,K-ATPase were ineffective with respect to GABA uptake (azabuperon, tetrabenazine). It is suggested that the drugs tested have at least two possible points of application: Na,K-ATPase and the hypothetical transmembrane carrier of GABA.Institute of Pharmacology, Academy of Medical Sciences of the USSR. Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 1, pp. 45–47, January 1976.     

Effect of GABA-ergic agents on the analgesic effect of morphine in rats

In order to detect possible interaction between GABA and opiates, the effects of GABA-ergic drugs on analgesia induced by morphine were studied. The vocalization response to electrical stimulation of the tail in rats was used as an index of the action of morphine. Thiosemicarbazide, an inhibitor of glutamate decarboxylase, and bicuculline, which blocks GABA-ergic receptors, drugs which, it is suggested, can be considered as a group of GABA-negative compounds, weaken and shorten the effect of morphine. Depakine, an inhibitor of -ketoglutarate-GABA-transaminase, like GABA itself, given in large doses (GABA-positive effects) strengthens morphine analgesia and prolongs its effect. The possible causes of these relations between GABA and opiates are discussed.Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 35–37, July, 1979.     

Ability of Fab-fragments of normal rabbit and human γ-globulins to inhibit blast transformation of human lymphocytes induced by phytomitogens

Monovalent and bivalent Fab fragments from normal human and rabbit -globulins were shown to suppress blast transformation of human lymphocytes induced by phytohemagglutinin and concanavalin A. The pepsin F(ab')₂ fragments obtained from highly purified rabbit antidinitrophenyl antibodies possess similar properties. An inhibitory action of the fragments was observed when they were added to the culture both simultaneously with and 24 and 48 h after the mitogen. The results may mean that suppression of lymphocyte transformation by fragments of -globulins is not due to their composition with the mitogens for receptors on the target cells; activity of the Fab fragment is evidently determined by structures located outside the combining site of the antibody.N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. Institute of Transplantation of Organs and Tissues, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 84, No. 8, pp. 178–181, August, 1977.     

Uptake of tryptophan by glial cells and synaptosomes of the rabbit cerebral cortex

The uptake of L-[¹⁴C]tryptophan by glial cells and synaptosomes of the rabbit cerebral cortex was investigated. The assimilation system of the glial cells exhibits high affinity for tryptophan (K_m=0.8 M). Tryptophan uptake by the synaptosomes has lower affinity (K_m=50 M). The psychotropic drugs chlorpromazine and imipramine inhibit glial uptake. The leading role of the glial cells in the nutrition of the neurons and the normal course of neurodynamic processes is confirmed.Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Department of Biochemistry, Tbilisi University. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 2, pp. 172–174, February, 1978.     

Mechanism of action of nonachlazine on nervous control over the coronary circulation

The new antiaginal drug nonachlazine, in experiments on anesthetized cats and dogs, inhibited the response of reflex decrease of the blood flow into the coronary arteries. In freely behaving cats nonachlazine also inhibited reflex changes in the blood flow in the system of the common carotid artery and reduced pressor vasomotor reflexes. Nonachlazine selectively inhibited vasoconstrictor impulses from A-afferent fibers of spinal nerves, i.e., it acts on the vasomotor component of the primary nociceptive response. This mechanism may perhaps lie at the basis of the relief of the pain syndrome by nonachlazine in ischemic heart disease.Laboratory of Pharmacology of the Cardiovascular System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 3, pp. 319–322, March, 1976.     

Effect of lithium hydroxybutyrate on cortical and subcortical excitability in rabbits

Microinjections of lithium hydroxybutyrate (10 g/l) had a depriming action on spontaneous cortical and subcortical electrical activity. The compound reduced the excitability of the motor cortex, hippocampus, caudate nucleus, thalamus, posterior hypothalamus, and mesencephalic reticular formation; the excitability of the amygdala was increased. In its depriming effect, lithium hydroxybutyrate surpassed lithium chloride.Department of Pharmacology, Tomsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 574–576, November, 1979.     

Uptake of GABA-3H by cortical glial cells and synaptosomes of rats receiving psychotropic drugs

Chlorpromazine noncompetitively inhibits the uptake of GABA-³H by both glial cells and synaptosomes, synaptosomal uptake being more sensitive to certain inhibitors. -Alanine competitively inhibits only the low-affinity GABA uptake system in the glial cells. Correlation is observed between inhibition of GABA uptake by psychotropic drugs in glial cells and synaptosomes. It is postulated that two different systems of GABA uptake with high and low affinity function in nerve endings and glial cells.Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Department of Biochemistry, Tbilisi University. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 561–563, May, 1977.     

Inhibition of serotonin uptake by synaptosomes and glial cells induced by certain drugs

Uptake of [¹⁴C]serotonin by glial cells and synaptosomes in the rabbit cerebral cortex was studied. The value of K_m for serotonin uptake was the same (0.083±0.02 M) for both synaptosomes and glial cells. Cortical synaptosomes took up serotonin twice as fast as glial cells (the rates of uptake were compared as protein). Of the psychotropic drugs tested, the most active inhibitors of both synaptosomal and glial serotonin uptake were the tricyclic antidepressant imipramine and the psychostimulant cocaine which, in concentrations of 50 M, inhibited uptake of [¹⁴C]serotonin in synaptosomes by 90% and in glial cells by 75–80%.Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Department of Biochemistry, Tbilisi University. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 564–566, November, 1979.     

Role ofβ-adrenoreception in realization of glycogenolytic and lipolytic effects of an excess of thyroid hormones

Experiments on rats showed that chronic administration of the -adrenoblocker propranolol in doses blocking glycogenolytic and lipolytic effects of exogenous adrenalin, does not prevent the fall in the glycogen level in the liver and myocardium and the rise in the serum free fatty acid level and in the lipolytic activity of adipose tissue in vitro arising under the influence of large doses of thyroxine.Laboratory of Pathological Physiology, Institute of Experimental Endocrinology and Hormone Chemistry, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 667–669, December, 1979.     

Role of histamine H2 receptors in the mechanism of formation of experimental gastric ulcers induced in rats by various stressors

Dystrophic lesions of the gastric mucosa were observed to be formed and the pepsinogen content was reduced by 57% in the gastric mucosa of rats exposed to various experimental stressors (immobilization with electrical stimulation, immobilization at 6°C, trauma to or ligation of the pylorus). and the changes correlated with the degree of injury to the stomach. Pharmacological blockade of H2 receptors by cimetidine (100 moles/kg) and methiamide (410 moles/kg) largely prevented the formation of experimental ulcers and the decrease in the pepsinogen level. The results indicate that endogenous histamine participates in the mechanism of formation of dystrophic gastric lesions.Department of Pharmacology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 8, pp. 151–153, August, 1979.     

Increased sensitivity of rabbit sensomotor cortical neurons to gaba produced by diazepam (microiontophoretic investigation)

Changes produced by diazepam in the effects of -aminobutyric acid (GABA), applied microiontophoretically to neurons of the rabbit sensomotor cortex, were investigated. Diazepam was shown to strengthen the inhibitory action of GABA on spontaneous unit activity and to prolong the effect of GABA on the duration of the inhibitory pause in unit responses to afferent stimulation and to direct cortical stimulation. Diazepam did not change unit responses to microiontophoretically applied glycine, glutamate, or acetylcholine. It is suggested that diazepam increases the sensitivity of the receptors of the postsynaptic membrane of neurons to GABA.Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 12, pp. 1448–1450, December, 1976.     

Role of injury in the appearance of “activated” smooth muscle cells

In experiments on rats the ultrastructure of the muscle tissue of the inferior vena cava after disturbance of the outflow of blood, of the muscular coat of the stomach after resection of 50% of its fundus, and of the muscular coat of the cecum after constriction of its ascending portion was studied. Activation of smooth muscles was shown to reflect the phase of injury to the ultrastructure of the cells, followed by processes of intracellular regeneration. Analysis of the ratio between DNA-synthesizing and activated cells showed the local origin of the latter from differentiated myocytes.Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR. No. 4 Main Board, Ministry of Health of the USSR. Institute of Human Morphology, Academy of Medical Sciences of the USSR. Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 7, pp. 112–115, July, 1977.     

Antagonistic effect of bicuculline and thiosemicarbazide on the tranquilizing action of diazepam

Bicuculline, a specific blocking agent of GABA-ergic receptors, in doses of 0.5 and 1 mg/kg (subcutaneously); and thiosemicarbazide, which inhibits GABA (-aminobutyric acid) synthesis in the brain, in doses of 5 and 8 mg/kg (subcutaneously); are antagonists of diazepam and weaken its tranquilizing action during conflict behavior in experimental rats. Bicuculline exhibits stronger antagonism toward diazepam than thiosemicarbazide. The results are evidence that GABA-ergic mechanisms may participate in the tranquilizing action of the benzodiazepines.Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 293–295, March, 1977.     

Role of the cholinergic and adrenergic systems of the hypothalamus in the regulation of pituitary adrenocorticotrophic function

In experiments on male rats the activity of the pituitary-adrenal system was studied after electrolytic destruction of different parts of the hypothalamus. Pharmacological analysis demonstrated the irregular distribution of cholinergic and adrenergic systems controlling the secretion of ACTH and glucocorticoids in the hypothalamus. It is suggested that the cholinergic systems are located in the mammillary region, -adrenergic systems in the region of the anterior or posterior hypothalamus, and -adrenergic receptors in the region of the ventromedial nuclei of the hypothalamus. The latter perhaps play an inhibitory role.Department of Pharmacology, Research Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 6, pp. 645–648, June, 1978.     

Analysis of the effect of amphetamine,L-dopa,and parachlorophenylalanine on the zoosocial behavior of isolated mice

Pathological changes in the structure of individual and zoosocial behavior of isolated mice were found under the influence of amphetamine, L-dopa, and parachlorophenylalanine. Deliberate strengthening of certain elements of the pathological isolation syndrome in mice with the aid of these drugs was found to be possible. Increasing or reducing contacts between animals of the same species can be used as an integrative indicator of the restorative (resocializing) or aggravating (desocializing) effects of psychotropic drugs on the pathology of animal behavior.Department of Pharmacology, I. P. Pavlov First Leningrad Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 4, pp. 311–314, April, 1979.     

Changes in blood cholesterol and triglyceride levels during self-stimulation and avoidance reactions

Change in the blood cholesterol and triglyceride levels during self-stimulation and avoidance reactions were studied in rabbits of both sexes. Self-stimulation was accompanied by a significant fall in the blood cholesterol and triglyceride levels. During the avoidance reaction the character of changes in the cholesterol level varied. In avoidance reactions of the aggression type the blood cholesterol was raised, whereas in reactions of the fear type it was lowered. The maximal deviation of the blood cholesterol from its initial level in all types of reactions was observed 15–30 min after stimulation.Laboratory of Physiology and Pathophysiology of the Circulation, All-Union Cardiological Scientific Center, Academy of Medical Sciences of the USSR. Laboratory of Neuronal Structure, Brain Institute, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. I. Chazov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 3, pp. 211–214, March, 1979.     

Effect of extremal stimulation on brain level of cyclic AMP

The content of cyclic adenosine-3,5-monophosphate (cAMP) in the brain was investigated after electrical stimulation of immobilized rats, leading to the development of degenerative lesions in the internal organs. A marked decrease was found in the cAMP content in the rats' brain, which appeared 15 min after the beginning of extremal stimulation and remained at the same level during stimulation for 3 h. The lowering of the cAMP level was evidently connected with a deficiency of noradrenalin and, perhaps, of other biologically active amines also in the brain during electrical stimulation.Laboratory of Experimental Pharmacology, Department of Pharmacology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 5, pp. 541–543, May, 1976     

Sensitivity to murine toxin and level of macrophagal 5′-nucleotidase activity

N. F. Gamaleya Research Institute of Epidemiology and Microbiology, Academy of Sciences of the USSR, Moscow. Mikrob Plague Research Institute, Saratov. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 3, pp. 297–299, March, 1992.     

Effect of succinic semialdehyde on some aspects of nitrogen metabolism in the brain tissue of hypoxic animals

Investigation of the concentrations of free ammonia, glutamine, and some free amino acids in the brain tissue of normal animals and of hypoxic animals receiving or not receiving succinic semialdehyde revealed a marked increased in the free ammonia and -alanine concentrations in hypoxia compared with normal, a small increase in the -aminobutyric acid, no change in the glutamic and aspartic acid concentrations, and a decrease in glutamine. If succinic semialdehyde was given before exposure to hypoxia the concentrations of free ammonia, glutamine, and -alanine were close to normal in this state. One possible mechanism of the antihypoxic effect of succinic semialdehyde is the conversion of this compound with the resulting synthesis of glutamic acid and glutamine, which leads to detoxication of the free ammonia that accumulates in the brain tissue during hypoxia.Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 5, pp. 539–541, May, 1976