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Biomedical subjects

D Samuel

Publications and source records attributed to D Samuel.

At least 271 records · Page 15Linked to original sources
PubMed1981

The effect of anti-synaptosomal membrane antibodies of neurotransmitter uptake.

Antibodies raised against synaptosomal plasma membranes of rat hippocampus (anti-HPC IgG) caused inhibition of [3H]noradrenaline, [3H]5-hydroxytryptamine, [3H]GABA and [3H]aspartate uptake into S1 fractions and slices of hippocampus and cerebral cortex, but not those of caudate nucleus and hypothalamus. Similar inhibition was not observed on using antibodies against synaptosomal membranes of rat caudate nucleus. Anti-HPC IgG raised against synaptosomal membranes of hippocampus failed to alter both spontaneous and K+-evoked release of [3H]noradrenaline. They did not interfere with the binding of [3H]desipramine (the potent noradrenaline-uptake inhibitor) and with the binding of [3H]dihydroalprenolol, thus excluding any interaction of the antibodies with drug receptors which are located on either the pre- or postsynaptic membrane. The anti-HPC IgG inhibit the enzymatic activity of [Na+-K+-]ATPase by 30% upon incubation of the antibodies with crude membrane preparations. A comparison of their inhibitory effects with those of the neurotoxin 6-hydroxydopamine suggests that the corresponding hippocampal specific antigens are located at a presynaptic site.

Animals↗
PubMed1980

The characterization and phosphorylation of an actin-like protein in synaptosomal membranes.

A protein of 43,000 daltons, named protein 'C', is a component of synaptosomal plasma membranes, vesicular and microsomal membranes, as well as synaptosomal and cellular cytoplasm. Protein 'C' undergoes endogeneous phosphorylation in synaptosomal plasma membranes but not in other subcellular fractions. This phosphorylation is stimulated by papaverine and calcium, inhibited by magnesium and not affected by cyclic nucleotides. Protein 'C' and muscle actin were shown to be very similar by isoelectric focusing, two dimensional gel electrophoresis, and by peptide mapping. This suggests that protein 'C' is an actin-like protein which undergoes endogenous phosphorylation specifically in synaptosomal plasma membranes. Phosphorylation of protein 'C' may be involved in neurotransmitter release.

Actins↗
PubMed1980

Lipid fluidity markedly modulates the binding of serotonin to mouse brain membranes.

The binding of [3H]serotonin to mouse brain crude membrane and synaptosomal membrane preparations was investigated as a function of membrane fluidity changes by lipids. The microviscosity (eta) of the synaptic membranes was increased by in vitro incubation with either cholesteryl hemisuccinate or stearic acid, resulting in an up to 5-fold increase in the specific binding of [3H]serotonin. Serotonin binding increased progressively until it reached a maximum at 1.75 relative eta units; then it declined. Fluidization of membrane lipids, by treatment with lecithin or linoleic acid, caused a small but significant decrease in serotonin binding. These observations are compatible with the concept of vertical displacement of membrane proteins, indicating that in the untreated brain tissue the accessibility (Bmax) of serotonin receptor binding sites constitutes only a fraction (about 20%) of the potential binding capacity stored in the membrane. Scatchard plots of [3H]serotonin binding, at different eta values, indicate a continuous change in the binding affinity (Kd) of serotonin to its receptor, concomitant with changes in its accessibility. These results may have important implications for physiological processes in the central nervous system, which are associated with modulation of membrane lipids, such as aging. In addition, the regional heterogeneity and plasticity of receptors may be accounted for by differences in membrane lipid fluidity. It was found here that various brain regions differ markedly in their membrane lipid viscosity.

Animals↗
PubMed1979

Sex differences in behavioral and thermal responses to pargyline and tryptophan.

The effects of parenterally injected pargyline and tryptophan on rectal temperature and behavior have been studied in male and female rats. Pargyline alone (50 mg/kg) produced hypothermia in both sexes. Pargyline (50 mg/kg) followed by low doses (20--50 mg/kg) of tryptophan caused a behavioral syndrome consisting of tremor, hindlimb abduction, forepaw treading, and straub tail. In females, but not in males, hypothermia was potentiated. The same dose of pargyline followed by higher doses (60--150 mg/kg) of tryptophan produced a short hypothermia followed by a dose-dependent behavioral syndrome, hyperthermia, and mortality. On all of these measures, females responded following shorter latencies and lower doses of tryptophan. Both hypothermia and hyperthermia were observed in treated animals following pretreatment with a peripheral decarboxylase inhibitor. The results suggest a complex role for serotonin in thermoregulation. The sex differences observed suggest higher activity of serotonin in female rat brains following the drug treatment, which may be accounted for by a higher utilization rate of tryptophan.

Animals↗
PubMed1979

Desmethylimipramine (DMI) counteracts learned helplessness in rats.

In a study of the mechanisms controlling the learned helplessness phenomenon, rats were exposed to either inescapable preshocks or control procedures, treated with one of three dosages of desmethylimipramine, and tested for later adaptive responding. This catecholamine modulator attenuated the deficits in escape responding that ordinarily follow prior exposure to inescapable preshocks, and it did so in a dose-dependent fashion. These findings support the position that the learned helplessness phenomenon is mediated by catecholamine changes.

Animals↗
PubMed1979

The in vivo distribution of an antidepressant drug (DMI) in male and female rats.

The accumulation of IP injected 3H-desipramine (DMI) in the brain and in the liver has been studied in both male and female rats. The total amount of DMI in the brains of females is 2 to 4 times that found in the brains of males. In females the amount of DMI is highest on the day of estrus and lowest on proestrus. This sex difference was not found following the injections of another psychoactive drug, 3H-chlorpromazine. In both males and females the level of DMI in the cortex and caudate is slightyl higher than in the hippocampus, septum and hypothalamus. The pharmaco-kinetics and dose dependence of the accumulation of DMI are also similar in males and females. Maximal levels are reached in the liver in less than 15 min, whereas in the brain it takes 30 min. The decline of radioactivity in the liver is faster than in brain. There is no saturation in the amount of DMI taken in brain. There is no saturation in the amount of DMI taken up in brain or liver in the dose range up to 40 mg/kg. The sex difference in the amount of 3H-DMI in brain, which may be the result of sex-dependent metabolism in liver microsomes, may explain the male-female differences in reaction to antidepressants.

Animals↗
PubMed1979

Uptake of fatty acids by cultured cardiac cells from chick embryo: evidence for a facilitation process without energy dependence.

Cultured heart cells from chick embryo accumulate fatty acids up to 50 fold at a steady-state level under defined conditions [ref.1]. Studies of fatty acid uptake as a function of different cellular parameters (intracellular ATP and pH, membrane potential and electrochemical gradients for monovalent and divalent cations) show the lack of effect of these factors. The rate of uptake is temperature-dependent. The maximum velocity V is affected with no change in the Km value of the saturable component; the activation energies were found to be 35.5 kJ.mol-1 for palmitate and 42 kJ.mol-1 for oleate. The results are in favour of a facilitation process which leads to an accumulation of fatty acids without energy dependence. The accumulation of fatty acids could be due to their association to intracellular membraneous and/or cytosolic components.

Acetates↗
PubMed1978

The in vivo binding of [3H]-desipramine and [3H]-chlorpromazine to areas in the rat brain.

The distribution of [3H]-desipramine (DMI) and of [3H]-chlorpromazine (CPZ) in rat brain was determined by the incorporation of radioactivity into various regions of the brain and by autoradiography of transverse cryostat sections. The label from [3H]-DMI was rapidly distributed in all brain regions, reaching peak levels within 30 min and considerably decreasing 1--4 h after injection. Following the selective destruction of catecholaminergic nerve terminals by intracerebral administration of 6-hydroxydopamine, a marked reduction in the incorporation of DMI, but not of CPZ, was evident in all brain areas investigated. The autoradiographed sections clearly demonstrated a preferential uptake of both drugs by the caudate nucleus. These findings suggest that DMI might be largely bound to presynaptic dopamine and norepinephrine terminals, while the CPZ binding involves postsynaptic sites.

Animals↗
PubMed1978

The role of serum albumin in the uptake of fatty acids by cultured cardiac cells from chick embryo.

Fatty acids enter the cultured cardiac cells from chicken embryo through two mechanisms, one involving a saturable process, the other resembling passive diffusion. Studies of the saturable component, at fixed concentrations of palmitate or of oleate and at increasing concentrations of albumin, show that this protein increases the rate of palmitate uptake with a maximum at palmitate/albumin molar ratios between 7 and 10 while it decreases the rate of oleate uptake under all conditions. Albumin cannot be replaced by other serum proteins; its effect is specific to saturated fatty acids, can be mimicked by the detergent Tween 40 and involves the binding of the fatty acid to the protein, prior to its delivery to the cell. Both with labelled saturated and unsaturated fatty acids the presence of albumin lowers the proportion of unesterified fatty acids and enhances the proportion of esterified fatty acids recovered in the cardiac cell after uptake. A similar effect of albumin was also found with hepatocytes and permanent cell lines. A specific role for serum albumin is presented, which assumes a 'dispersing' effect of this protein towards dimers (or higher aggregates) of saturated fatty acids and the entry of fatty acids into the cell as monomers.

Animals↗
PubMed1978

Effect of maternally administered sodium nitrite on hepatic erythropoiesis in fetal CD-1 mice.

A commonly used food preservative, sodium nitrite, was administered to pregnant CD-1 mice at a concentration of 0.5 mg/mouse/day. Embryotoxic and teratogenic effects on the hemopoietic tissues and skeletons of their offspring, were evaluated. Fetal mortality, resorptions, the mean number of offspring per litter, the mean weight per embryo and the incidence of skeletal malformations, were not significantly different from controls. Hemopoietic cell suspensions, prepared from the livers of treated and control 14-, 16- and 18-day embryos, were cytocentrifuged onto microscope slides and differential counts were performed after staining with benzidine and Wright-Giemsa stain. The results indicate that maternally administered Na nitrite, stimulates fetal hepatic erythropoiesis. This was manifested in a statistically significant increase in the percentage of polychromatophilic erythroblasts and mature erythrocytes at 14 and 16 days of gestation, respectively. The possibility that Na nitrite may induce fetal methemoglobinemia is discussed and mechanisms responsible for the observed erythroid stimulation, are considered.

Animals↗