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Biomedical subjects

R Weizman

Publications and source records attributed to R Weizman.

At least 19 recordsLinked to original sources
PubMed1992

Chronic ethanol consumption and withdrawal affects mitochondrial benzodiazepine receptors in rat brain and peripheral organs.

Ethanol administration to rats for 30 days resulted in a significant decrease (-28%; P < 0.05) in the density of mitochondrial benzodiazepine receptors (MBR) in the olfactory bulb. The reduction in [3H]PK 11195 binding persisted 24 hr after cessation of alcohol and had returned to normal values when measured 4 days later. Alterations were confined to this brain region and were not detected in the cerebral cortex, cerebellum or hippocampus. [3H]PK 11195 binding was elevated in the liver (100%; P < 0.01), heart (43%; P < 0.01) and testis (27%; P < 0.05) 30 days following ethanol consumption and this persisted for 1 and 4 days after abrupt withdrawal. A transitory decrease (-20%; P < 0.05) in MBR density was observed in the adrenal gland following 30 days of alcohol ingestion, but disappeared during withdrawal. The alterations in these receptors may be relevant to the cellular damage or dysfunction induced by chronic exposure to ethanol.

Alcohol Drinking↗
PubMed1992

Platelet imipramine binding and plasma cortisol levels in Israeli civilians during the Gulf War.

[3H] Imipramine binding to platelets and plasma cortisol levels were measured in nine Israeli civilians before, during, and after repeated missile attacks. Hamilton Anxiety Rating Scale (HARS), and Beck Depression Inventory (BDI) were similar before and during the war and decreased significantly after the war. A trend toward increase in platelet imipramine binding values was observed during the war when compared with the postwar values (19%; p = 0.056), and/or when compared with prewar values (26%; p = 0.063). However, one-way analysis of variance with repeated measures did not reveal a significant statistical difference [F (2,6) = p = 2.07; NS] among the three time points. A significant correlation was found between HARS score, but not BDI, and imipramine binding values in the prewar and postwar time points (r = 0.87; 0.71, respectively). Plasma cortisol levels did not alter significantly during the study period.

Adjustment Disorders↗
PubMed1992

Immunomodulatory effect of peripheral benzodiazepine receptor ligands on human mononuclear cells.

Immunomodulatory effect of ligands active at the peripheral benzodiazepine receptor (PBR) was examined in human peripheral blood mononuclear cells (PBMC). Ro5-4864, PK11195 and diazepam suppressed phytohemagglutinin (PHA) and concanavalin A (ConA) induced proliferation of PBMC. All three ligands inhibited interleukin-3-like activity (IL-3-LA) secretion, while the production of interleukin-2 (IL-2) was inhibited by Ro5-4864 and diazepam only. The selective central benzodiazepine ligand clonazepam did not affect the cellular immune functions examined. Our results indicate an in-vitro immuno-suppressive activity of peripheral and mixed, but not central type benzodiazepine ligands.

Adjuvants, Immunologic↗
PubMed1992

Biochemical, physiological, and pathological aspects of the peripheral benzodiazepine receptor.

The PBR is a mitochondrial protein composed of at least two subunits, an approximately 30-kDa subunit that contains the site for BZs and an approximately 18-kDa subunit that binds isoquinoline carboxamide derivatives. Porphyrins and diazepam binding inhibitor are putative endogenous ligands for these receptors, which are under neural and hormonal control. Alterations in the density of PBR seem to be a sensitive indicator of stress: up-regulation after acute stress and down-regulation induced by repeated stress. PBR-specific ligands are involved in the control of cell proliferation and differentiation, and their binding is increased in some cancer tumors. Numerous studies in various endocrine organs have revealed that PBR are located in specific regions or tissues in the organs. Furthermore, PBR densities in various organs subject to hormonal control are regulated by organotropic hormones. At least in some cases, BZ ligands do not exert a specific effect in an organ, but rather modulate the well-documented effects of that particular hormone. To the best of our knowledge, BZ ligand action in peripheral tissues is dependent on recognition of PBR, which may suggest a receptor-mediated action.

Animals↗
PubMed1992

Ontogenesis of peripheral benzodiazepine receptors: demonstration of selective up-regulation in rat testis as a function of maturation.

Peripheral benzodiazepine receptors (PBR) have been localized to the outer mitochondrial membrane in a variety of organs, where they apparently play a role in steroidogenesis, oxidative processes, and/or growth and development. Previous studies have demonstrated ontogenetic changes in heart and lung PBR, with maximal PBR density at 31 days, as opposed to negligible changes in brain PBR during the prenatal through postnatal periods. The present study was designed to examine the influence of maturation and aging upon PBR binding characteristics. Rats aged 1, 2, 12, 18, and 24 months were sacrificed, and the following organs were removed according to standard protocol: heart, lungs, kidneys, adrenal gland, and testes. Binding studies were performed using [3H]PK 11195 as a radioligand. A 3-fold increase in PBR density was demonstrated in testis during maturation, with maximal values appearing at 18 months, followed by a decline at 24 months. None of the other organs examined showed significant changes in PBR density. No alterations were observed in affinity values for the various organs and ages. Since testicular PBR are putatively involved in testosterone production, these results might reflect critical interactions between PBR and gonadal hormone activity during development.

Adrenal Glands↗
PubMed1992

Disulfiram and diethyldithiocarbamate are competitive inhibitors at the peripheral benzodiazepine receptor.

In the present study in vitro interactions of disulfiram (an agent used to induce ethanol intolerance in alcoholics), diethyldithiocarbamate (DDC), and metronidazole with central benzodiazepine receptors (CBR) and peripheral benzodiazepine (BZ) receptors (PBR) were investigated in rat tissues. Disulfiram displaced specific binding of [3H]PK 11195 from PBR in the cerebral cortex with an IC50 value of 5 x 10(-7) M. The binding of [3H]PK 11195 and [3H]Ro 5-4864 to PBR in the kidney was displaced by disulfiram with IC50 values of 7 x 10(-7) and 2 x 10(-7) M, respectively. DDC displaced [3H]PK 11195 binding to kidney membranes with an IC50 value of 5 x 10(-5) M. Binding of [3H] flunitrazepam to CBR in the cerebral cortex was not affected by either disulfiram or DDC. Metronidazole (up to 10(-4) M), a disulfiram congener, did not affect [3H]flunitrazepam (FNZ) and [3H] PK 11195 binding to CBR and PBR, respectively. Scatchard analysis of [3H]PK 11195 binding to kidney membranes, performed in the absence or presence of 7 x 10(-7) M disulfiram, decreased ligand affinity without influencing the maximal number of binding sites, suggesting a competitive inhibition. Beta-Mercaptoethanol (2 x 10(-2) M), which blocks the inhibitory activity of disulfiram and DDC at the acetaldehyde dehydrogenase, did not affect the inhibitory potency of disulfiram at the kidney PBR. Removal of disulfiram from kidney by repeated washing with Tris-HCl buffer resulted in the restoration of binding properties to control values, suggesting reversibility of disulfiram binding to PBR.

Animals↗
PubMed1991

Testosterone and cyproterone acetate modulate peripheral but not central benzodiazepine receptors in rats.

Sixteen days of testosterone acetate (TA) treatment in male rats induced an increase in the densities of peripheral benzodiazepine receptors (PBR) in the adrenal and Cowper's glands and a decrease in PBR density in the testis. TA did not alter PBR density in the heart, cerebral cortex, or pituitary, or central benzodiazepine receptor (CBR) density in the cerebral cortex or hypothalamus. The antiandrogenic agent cyproterone acetate induced a decrease in PBR density in the testis, adrenal, and pituitary, but did not affect PBR density in Cowper's glands, heart, or cerebral cortex, or CBR density in the cerebral cortex or hypothalamus. In all of the above organs, affinity values did not change following the treatment with both agents. The receptoral changes may be relevant to the physiological and neurobehavioral effects of the chronic exogenous androgenic and antiandrogenic treatment.

Androgen Antagonists↗
PubMed1991

Effects of uncomplicated acute myocardial infarction on biochemical parameters of stress and sexual function.

The blood levels of several "stress indicators" (prolactin [PRL], growth hormone [hGH], total catecholamines, and adenosine 3',5'-cyclic monophosphate [cAMP]) were measured in men during the first 2 weeks of uncomplicated acute myocardial infarction (AMI) and during a 3-month follow-up period. PRL levels were significantly elevated during the first day, and hGH was elevated during the week after the AMI. The levels returned to the control baseline values thereafter. The levels of the total catecholamines and cAMP in blood remained normal throughout the study period. Sexual function during the 3-month follow-up was measured in 29 patients, using a specially designed questionnaire. Impotence was found in five patients and decreased libido in four. No correlation was noted between PRL values, the other stress indicators, and sexual dysfunction. A trend toward increased incidence of sexual dysfunction was found among patients with recurrent AMI.

Adult↗
PubMed1990

Adrenalectomy prevents the stress-induced decrease in in vivo [3H]Ro15-1788 binding to GABAA benzodiazepine receptors in the mouse.

The effect of a single or repeated swim stress on in vivo benzodiazepine receptor binding to various brain regions in adrenalectomized and sham-operated (control) mice was assessed using the benzodiazepine receptor antagonist, [3H]Ro15-1788. In sham-operated mice the binding of [3H]Ro15-1788 to benzodiazepine receptors was reduced in the hippocampus and hypothalamus (single or repeated stress) and cerebral cortex (repeated swim stress) compared to non-stressed mice. In contrast, no alterations in [3H]Ro15-1788 binding were observed in any brain region in adrenalectomized mice after either single or repeated swim stress. These data suggest that an intact hypothalamic-pituitary-adrenal axis is required for the stress-induced decrease in benzodiazepine receptor occupancy measured using the in vivo binding method.

Adrenalectomy↗
PubMed1990

Immunoreactive beta-endorphin, cortisol, and growth hormone plasma levels in obsessive-compulsive disorder.

Basal morning plasma levels of immunoreactive-beta-endorphin (ir-beta-EP), cortisol, and growth hormone (GH) were assessed in 13 obsessive-compulsive disorder (OCD) patients in comparison to 20 healthy controls. All subjects were drug free for at least 1 year. The mean plasma level of ir-beta-EP was significantly lower (36%) in the OCD patients when compared with the control subjects. The decrease in ir-beta-EP was not accompanied by alteration in cortisol and GH plasma levels.

Adolescent↗
PubMed1989

Stress-induced behavioral depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy.

Rats exposed to inescapable tailshock exhibit deficits in learning a simple shuttlebox escape task 24 h later. This syndrome has been termed 'behavioral depression' or 'learned helplessness', and is a model of stress-induced depression. In the present study a significant (25%) decrease in GABA receptor-mediated chloride ion flux as measured by muscimol-stimulated 36Cl- uptake in synaptoneurosomes was found in the cerebral cortices of rats that failed the shuttlebox task as compared to naive control rats. Rats which were exposed to tailshock and subsequently learned the escape task did not show a significant difference in muscimol-stimulated 36Cl- uptake as compared to naive control rats. Similarly, rats that failed to learn the shuttlebox escape task had significantly lower in vivo [3H]Ro15-1788 specific binding in cerebral cortex (43%), hippocampus (35%) and striatum (33%) as compared to naive control rats. In cerebellum and hypothalamus, there were significant reductions in specific [3H]Ro15-1788 binding in both animals that failed and animals that learned the shuttlebox escape task as compared to naive controls. To control the stress of the footshock associated with the shuttlebox escape task, we investigated the effect of gridshock in which total footshock received was equivalent to that received by rats who failed the shuttlebox task. There were no differences in muscimol-stimulated 36Cl- uptake or in vivo [3H]Ro15-1788 specific binding between naive controls and rats administered footshock independent of a learning task. These data suggest that the development of stress-induced behavioral depression may be associated with a decrease in GABA receptor-mediated chloride channel function.

Animals↗
PubMed1989

Chronic diazepam treatment induces an increase in peripheral benzodiazepine binding sites.

The effect of chronic (21 days) diazepam treatment (0.5 mg/kg, intraperitoneally) on [3H]PK 11195 binding to the heart and cerebral cortex was studied. A significant increase in the density of peripheral benzodiazepine binding sites in the heart (18%) and cerebral cortex (19%) was observed. Following five days of withdrawal, the maximal binding capacity of these sites returned to normal control values. No alteration in the equilibrium dissociation constant was observed during the treatment and withdrawal period.

Animals↗
PubMed1989

Effects of chronic chlorpromazine treatment on peripheral benzodiazepine binding sites in heart, kidney, and cerebral cortex of rats.

Daily intraperitoneal administration to rats of 5 mg/kg of chlorpromazine (CPZ) for 21 days induced a significant up-regulation (51%) of peripheral benzodiazepine binding sites (PBSs) in cerebral cortex and a down-regulation of PBSs in the heart (25%) and kidney (14%), whereas no alteration in [3H]flunitrazepam binding in cerebral cortex was observed. [3H]PK 11195 binding to cerebral cortex returned to normal following 5 days of CPZ withdrawal, whereas the density of PBSs in the heart and kidney remained reduced. The affinity of PBSs for the ligand [3H]PK 11195 in the cerebral cortex and heart was not affected by the drug treatment or withdrawal. The CPZ-induced alterations in PBSs may be relevant to the effects of the drug on CNS and/or peripheral organs.

Animals↗
PubMed1989

Repeated swim stress alters brain benzodiazepine receptors measured in vivo.

The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of [3H]Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in [14C]iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress [an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures], although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

Animals↗
PubMed1988

Increase in central and peripheral benzodiazepine receptors following surgery.

[3H]Flunitrazepam, [3H]PK 11195, [3H]quinuclidinyl benzilate (QNB) and monoamine oxidase (MAO) A and B activity were measured in male rats 1, 3 and 7 days following laparotomy. The surgery resulted in the up-regulation of central benzodiazepine (BZ) receptors in cerebral cortex and of peripheral BZ binding sites in brain and kidney on the first and third days after operation. This increase was followed by a decrease to normal range 7 days after the surgical procedure. [3H]QNB binding to muscarinic receptors in the cerebral cortex as well as MAO A and B activity in rat cerebral cortex and kidney were not affected by the surgical manipulation. The modulatory effect of surgery on BZ receptors corresponds to stages of the healing process in surgical wounds.

Animals↗