Subir K. Chanda

Cocaine andd-amphetamine induce changes in central ß-adrenoceptor sensitivity: Effects of acute and chronic drug treatment

The effects of acute and chronic treatment with psychomotor stimulants on specific binding of [3H]dihydroalprenolol to beta-adrenoceptors in rat brain were examined. At a dose of 10 mg/kg both acute and chronic treatment with cocaine and chronic treatment with D-amphetamine (10 mg/kg) caused increased binding of [3H]dihydroalprenolol. The molecular mechanism for this enhanced binding appears to be augmentation of the density of beta-adrenoceptors in rat brain. At a lower dose (5 mg/kg), however, chronic administration of D-amphetamine caused a decrease in the density of beta-adrenoceptors in rat brain. Chronic treatment with either D-amphetamine (10 mg/kg) or cocaine induced a marked increase in the magnitude of cyclic AMP accumulation in rat brain slices elicited by norepinephrine. Acute as well as chronic administration of D-amphetamine in vivo inhibited the temperature-dependent uptake of [3H]norepinephrine in rat brain synaptosomal homogenates, but no such inhibition was observed after chronic or acute treatment with cocaine. The results suggest that psychomotor stimulants induce beta-adrenoceptor supersensitivity which may be involved in the phenomenon of reverse tolerance and possibly psychosis in humans. The development of beta-adrenoceptor supersensitivity does not appear to be mediated through alterations in norepinephrine transport at the presynaptic sites.

Amphetamine induces beta-adrenergic receptor supersensitivity.

THE interactions of amphetamines and catecholamines in the peripheral sympathetic nervous system and in the brain have been widely studied. Amphetamines have been reported to mimic catecholamines at their receptor sites1–3, inhibit monoamine oxidase4, impair reuptake mechanism for the catecholamines5 and to directly release catecholamines into the synaptic cleft6. Although the consensus of the available literature indicates that d-amphetamine indirectly stimulates catecholamine postsynaptic receptors by increasing the release and blocking the reuptake of catecholamines7,8, the question whether dopamine, noradrenaline or both, are of importance for the central actions of d-amphetamine is controversial7,8. Recently, α-adrenergic9, β-adrenergic10–13 and dopaminergic14,15 receptors in brain tissue have been successfully identified by measuring the binding of radiolabelled ligands to specific receptor sites. Availability of such methods has permitted the examination of the effects of acute and chronic administration of psychotropic drugs on the postsynaptic catecholaminergic receptors in brain tissue13,16. We report here the effects of acute and chronic administration of d-amphetamine on the postsynaptic β-adrenergic receptors in rat brain.

Isolation and partial characterization of a mercury-binding nonhistone protein component from rat kidney nuclei

A nonhistone protein component (NHPIns) firmly bound to DNA of rat kidney nuclei has been isolated and partially characterized. In vivo studies show that this protein specifically incorporates 35 to 45 times more 203Hg than any other nuclear protein fractions. No difference in the ratio of NHPIns to DNA between normal and mercury-poisoned rat kidney nuclei was observed. NHPIns protein gives a single major band by sodium dodecyl sulfate gel electrophoresis. Electrophoretic pattern as well as amino acid composition of this protein isolated from both normal and mercurypoisoned rats are also found to be similar. Cysteine content is 1.3 to 1.4 mole per cent.

The structure of higher eukaryotic chromosomes

Abstract Chromosomal structure has been analyzed from the standpoint of core structure and the relationship between interphase and metaphase chromosomal forms. A possible relationship between prokaryotic and eukaryotic chromosomes has also been proposed. The general structural plan offered is a series of DNA-histone loops extending laterally from a core held together by disulfide bond linkages. The models proposed have been derived from a loop model with core very recently proposed by H. Sobell. A short experimental section of this paper demonstrates that S-S cleaving agents as well as trypsin cause easily observable effects on human metaphase chromosomes.

Ratios of protein fractions to DNA and electrophoretic studies of histones of diploid and polyploid nuclei of rat liver

Abstract Diploid and polyploid nuclei have been isolated from the livers of 3–4-month-old rats. The extent of contamination of each fraction with the other fraction being probably not above 10%, as shown by microscopic counting and analyses of DNA per nucleus. (The average amount of DNA per diploid nucleus was 5.5 pg and per polyploid nucleus was 12.8 pg.) No differences could be established in the ratios of the globulin fraction, total histone, or residual proteins to DNA for the two classes of nuclei. The disc-gel electrophoretic patterns and analyses of histones for amino acids were also the same for diploid and polyploid nuclei.

β-ADRENOCEPTOR SENSITIVITY FOLLOWING PSYCHOTROPIC DRUG TREATMENT

Chronic administration of antidepressants led to a decrease in the density of βAR in rat brain. In contrast, psychomotor stimulants induce an enhancement of βAR levels. Only desipramine, doxepin and amphetamine inhibited norepinephrine (NE) uptake. Although the level of NE may have an important role in controlling βAR density, this is not the only mechanism for the regulation of βAR concentration.

Separation of histones from normal rat liver nuclei into easily extractable and residual histone and characterization of the fractions

Abstract The total histone of normal rat liver nuclei has been separated into an easily extractable histone fraction (H e ) and the residual histone (H r ) by rapidly lowering the pH of the nuclei (after removing the globulin fraction) to pH 2.8–2.9 in order to remove H e . H r is then recovered by extracting the nuclei with dilute HCl. The H e and H r fractions have been compared with the total histone extract (H t ) by disc gel electrophoresis, using Gilford scanning of the gels and resolving the curves with a Dupont curve analyzer. Two histone bands appear in H e [F1 and F2(a)2]. H e and H r have also been characterized by amino acid composition. The ratio of H t to DNA (dry weight) is approximately 2, while H e /DNA = ca . 0.84 and H r /DNA = ca . 1.04. Ammonia-soluble histone is electrophoretically identical with H e . The histone lost when nuclei are isolated in CaCl 2 - or MgCl 2 -sucrose solutions is not electrophoretically identical with H e , since the histone that remains gives an electrophoretic pattern which is identical with that of H t .

A simple method for the crystallization of beef liver crotonase.

Abstract A very simple method for crystallizing crotonase from small or large batches of beef liver is described which is based on the finding that the second crystalline beef liver protein of Dounce and Sumner (Dounce, A. L. and Sumner, J. B. (1938) J. Biol. chem. 124, 418–451) is crotonase. Dioxane is used for extracting and crystallizing the enzyme. Identification of the crystalline liver protein as crotonase is based on its crotonase activity, sedimentation constant, electrophoretic properties, amino acid analysis, methods of recrystallization, and crystalline form.

A comparative study of hagfish and rat liver histones

Abstract 1. 1. Histones from hagfish (Polistotrema politrema) and rat (Rattus norvegicus) were studied by molecular exclusion chromatography, disc-gel electrophoresis and amino acid analysis. 2. 2. The histone : DNA ratio and the proteolytic activity associated with the nuclei in the two species were also determined. 3. 3. Sephadex G-200 elution profiles of hagfish whole histone were similar in the number of peaks to those reported for rat liver histones. 4. 4. Quantitative differences were found in the electrophoretic patterns of lysine-rich (F1) histones of these two unrelated species. 5. 5. The histone : DNA ratio was found to be the same (i.e. 2) in these two vertebrates.