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Biomedical subjects

B Tabakoff

Publications and source records attributed to B Tabakoff.

At least 73 records · Page 4Linked to original sources
PubMed1993

Association of monoamine oxidase (MAO) activity with alcoholism and alcoholic subtypes.

A familial/genetic study of platelet monoamine oxidase (MAO) activity in alcoholics was carried out. MAO activities were determined using phenylethylamine (PEA) as substrate at Km concentration (1.2 microM) and at saturating concentration (12.0 microM). Complex segregation analysis of familial data indicated a single major gene mode of transmission of activity at both substrate concentrations. In addition, the present sample size (13 families, 108 members) proved sufficient to allow correlation analysis of enzyme activity with affection status and clinical subtypes of affecteds. MAO activity was significantly correlated with alcoholism at both Km and saturating substrate concentrations and a significant correlation between low MAO activity and Cloninger Type II alcoholism was seen at Km substrate concentration. These results confirm a hierarchical cosegregation of platelet MAO activity and alcoholism suggesting that MAO activity warrants continued status as a marker in alcoholism.

Adult↗
PubMed1993

Glutamate-induced neurotoxicity is increased in cerebellar granule cells exposed chronically to ethanol.

Chronic exposure of primary cultures of cerebellar granule cells to ethanol has previously been shown to result in an enhanced response of the cells to N-methyl-D-aspartate (NMDA). To determine if this increase in NMDA receptor function alters glutamate-induced cytotoxicity, cells were incubated in the presence or absence of 100 mM ethanol for 3 days, the ethanol was removed, the cells were treated with glutamate, and cell survival was assessed with fluorescein diacetate fluorescence. The ethanol-treated cells showed a significantly increased cytotoxic response to glutamate. Treatment with receptor-selective antagonists demonstrated that the cytotoxicity was mediated by NMDA receptors. The increased vulnerability to glutamate-induced cytotoxicity in ethanol-exposed cells may underlie the neuronal degeneration observed in animals and humans after chronic ethanol intake and withdrawal.

Animals↗
PubMed1993

A novel adenylyl cyclase sequence cloned from the human erythroleukemia cell line.

The polymerase chain reaction (PCR) was used to detect several forms of adenylyl cyclase (AC's) expressed in human erythroleukemia (HEL) cells. Degenerate oligonucleotide primers were synthesized based on the conserved sequences in the C2a area of the AC's. HEL cells were found to contain mRNA for type III and type VI AC. In addition, a novel AC message was identified. The cloned sequence, excluding primer areas, represented 69 amino acids with most similarity to rat AC's II and IV. Northern analysis of RNA from HEL cells demonstrated a 6.7 kilobase message. RNase protection assays revealed that in HEL cells the novel AC mRNA was dominant compared to types III and VI. Human embryonic kidney cells (HEK293) were also used a source of mRNA to synthesize cDNA for PCR reactions. The HEK293 cells were found to contain message corresponding to type II, III, VI AC as well as the novel AC message. The novel AC message was also detected in human brain tissue and was most abundant in the caudate, cerebellum and hippocampus. The smallest amount of novel AC mRNA in the tested brain tissue was found in the cortex. The mRNA for the novel AC was relatively abundant in human liver.

Adenylyl Cyclases↗
PubMed1993

Radioligand binding to the N-methyl-D-aspartate receptor/ionophore complex: alterations by ethanol in vitro and by chronic in vivo ethanol ingestion.

The effects of ethanol on the binding of [3H]MK-801, [3H]L-glutamate, [3H]glycine and [3H]CGS 19755 to the N-methyl-D-aspartate receptor were determined in membranes from mouse cortex and hippocampus. Under equilibrium conditions, ethanol in vitro (100 mM) did not alter the apparent affinity or binding site density for any of these ligands. However, in the presence of glutamate and the selective glycine antagonist, 5,7-dichlorokynurenic acid, ethanol inhibited the non-equilibrium binding of [3H]MK-801. This inhibition could be reversed in a time- and concentration-dependent manner by addition of glycine. These data suggest that ethanol may inhibit N-methyl-D-aspartate receptor-mediated responses by altering the kinetics of channel activation. Chronic in vivo ethanol ingestion by mice, that resulted in tolerance to and physical dependence on ethanol, produced an increased density of hippocampal [3H]MK-801 and [3H]L-glutamate binding sites, but not [3H]glycine or [3H]CGS 19755 binding sites. It is possible that chronic ethanol ingestion may influence the subunit composition of the NMDA receptor complex.

Alcoholism↗
PubMed1993

Chronic barbiturate treatment increases NMDA receptors but decreases kainate receptors in mouse cortex.

Chronic phenobarbital effects on brain NMDA and kainate receptors were assessed using [3H]MK-801 and [3H]kainate. Mice fed a phenobarbital diet for 7 days had a higher density of MK-801 binding sites (NMDA receptors) but a lower density of kainate receptors in cortex than control mice. No changes in MK-801 or kainate binding were observed in hippocampus. The results suggest brain area specific adaptation of certain glutamate receptors to chronic barbiturate treatment.

Animals↗
PubMed1993

Ethanol, sedative hypnotics, and glutamate receptor function in brain and cultured cells.

Ethanol, acutely, is a potent and selective inhibitor of the function of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in primary cultures of cerebellar granule cells. The effect of ethanol can be reversed by high concentrations of glycine, and nonequilibrium ligand binding studies in brain membrane preparations suggest that ethanol may act by decreasing the frequency of ion channel opening. After chronic consumption of ethanol by animals, the number of NMDA receptors (measured by ligand binding) is increased in many brain areas. Similarly, NMDA receptor function is increased in cerebellar granule cells exposed chronically to ethanol. In the intact animal, this receptor up-regulation may be associated with ethanol withdrawal seizures, which are attenuated by uncompetitive antagonists at the NMDA receptor. In contrast to ethanol, barbiturates have a greater inhibitory effect at the kainate subtype of glutamate receptor than at the NMDA receptor. After chronic barbiturate ingestion, kainate binding is decreased in certain brain areas, while ligand binding to the NMDA receptor is increased. Overall, the pattern of brain area-specific effects of barbiturates on NMDA and kainate receptor function is quite distinct from that of ethanol.

Alcoholism↗
PubMed1993

Ethanol, sedative hypnotics and glutamate receptor function in brain and cultured cells.

Ethanol, acutely, is a potent and selective inhibitor of the function of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in primary cultures of cerebellar granule cells. The effect of ethanol can be reversed by high concentrations of glycine, and non-equilibrium ligand binding studies in brain membrane preparations suggest that ethanol may act by decreasing the frequency of ion channel opening. After chronic consumption of ethanol by animals, the number of NMDA receptors (measured by ligand binding) is increased in many brain areas. Similarly, NMDA receptor function is increased in cerebellar granule cells exposed chronically to ethanol. In the intact animal, this receptor up-regulation may be associated with ethanol withdrawal seizures, which are attenuated by uncompetitive antagonists at the NMDA receptor. In contrast to ethanol, barbiturates have a greater inhibitory effect at the kainate subtype of glutamate receptor than at the NMDA receptor. After chronic barbiturate ingestion, kainate binding is decreased in certain brain areas, while ligand binding to the NMDA receptor is increased. Overall, the pattern of brain area-specific effects of barbiturates on NMDA and kainate receptor function is quite distinct from that of ethanol.

Alcoholism↗
PubMed1993

Bicuculline-produced regional differences in the modulation of 35S-TBPS binding by GABA, pentobarbital and diazepam in mouse cerebellum and cortex.

The modulation of 35S-t-butylbicyclophosphorothionate (35S-TBPS) binding by in vitro addition of gamma-aminobutyric acid (GABA), diazepam, pentobarbital, etomidate and etazolate was studied in the presence of KCl (100 mM) in the cerebellum and in the cortex of C57Bl mice. In the cortex, all of the depressant drugs caused a biphasic effect (stimulation followed by inhibition) on 35S-TBPS binding, whereas in the cerebellum only inhibition was observed. Saturation analysis revealed that the enhancement of 35S-TBPS binding was due to an increase in the affinity of 35S-TBPS for its binding sites. The introduction of a GABAA receptor antagonist, bicuculline methiodide (10 microM), into assay media altered the effects of the depressants, except for those of diazepam, on 35S-TBPS binding in a complex manner. Our results indicate that bicuculline, in addition to its GABAA receptor blocking properties, also influenced the binding of 35S-TBPS through some other, as yet unknown, mechanism(s). Thus, bicuculline not only produced a rightward shift of the dose-response curves of the central depressant drugs in the cortex, but also increased the maximal stimulation of 35S-TBPS binding. Furthermore, in the cerebellum, the previously observed drug-induced inhibition of 35S-TBPS binding was replaced by stimulation followed by inhibition in the presence of bicuculline. Finally, it was found that the in vitro addition of bicuculline had no effect on the diazepam-induced stimulation of 35S-TBPS binding. It is suggested that the regional differences in the modulation of 35S-TBPS binding in various brain structures may be due to endogenous differences in the molecular composition of GABAA receptors in various brain areas.

Animals↗
PubMed1992

Chronic exposure of cerebellar granule cells to ethanol results in increased N-methyl-D-aspartate receptor function.

In primary cultures of cerebellar granule cells, activation of the N-methyl-D-aspartate (NMDA) receptor leads to Ca2+ influx. Previous work showed that this response is selectively inhibited by acute exposure to low concentrations of ethanol. The present results demonstrate that the response to NMDA (measured as an increase in intracellular Ca2+ concentration, using fura-2 fluorescence) is significantly enhanced after chronic in vitro exposure of the cells to ethanol (100 mM for 2-4 days; 20 mM for 3 or more days). This enhancement is consistent with an increased number of NMDA receptors, with no change in receptor properties. Specifically, there was no change in the EC50 values for NMDA and glycine or in the magnitude of inhibition of the NMDA response by competitive or uncompetitive antagonists. There was also no change in the ability of acute ethanol to inhibit the NMDA response after chronic exposure of the cells to ethanol. Furthermore, chronic ethanol exposure did not alter depolarization-dependent increases in intracellular Ca2+ observed after exposure of the cells to 30 mM KCl. The data suggest that chronic ethanol exposure produces a selective up-regulation of NMDA receptor function. In the intact animal, such a change may be associated with particular symptoms of ethanol withdrawal, i.e., withdrawal seizures.

Amyloid beta-Protein Precursor↗
PubMed1992

Comparison of the effects of the uncompetitive N-methyl-D-aspartate antagonist (+-)-5-aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (ADCI) with its structural analogs dizocilpine (MK-801) and carbamazepine on ethanol withdrawal seizures.

The ability of [(+-)-5-aminocarbonyl-10,11-dihydro-5H-di-benzo [a,d]cyclohepten-5,10-imine (ADCI) and its structural analogs dizocilipine (MK-801) and carbamazepine to block ethanol withdrawal seizures was tested in mice made physically dependent upon ethanol. Three injections of either ADCI (ranging from 1.0-10.0 mg/kg), dizocilpine (ranging from 0.1-1.0 mg/kg) or carbamazepine (ranging from 17-50 mg/kg) were administered during the first 7 hr of ethanol withdrawal. The severity of ethanol withdrawal seizures was rated during the first 11 hr of withdrawal and again at 24 hr after withdrawal of ethanol. ADCI and dizocilpine suppressed the severity and occurrence of the withdrawal seizures in a dose-dependent fashion, whereas carbamazepine was ineffective in blocking the withdrawal seizures. The relative potencies of dizocilpine, ADCI and carbamazepine in suppressing ethanol withdrawal seizures corresponded with the relative potencies of the compounds in displacing [3H]dizocilpine from mouse cortical membrane preparations. These findings are consistent with the suggestion that blockade of N-methyl-D-aspartate-mediated neurotransmission is an effective treatment for decreasing ethanol withdrawal seizures. ADCI also blocked the occurrence of withdrawal-associated whole body tremors, whereas dizocilpine and carbamazepine were ineffective in blocking the tremors. The doses of ADCI, dizocilpine and carbamazepine that resulted in motor incoordination on an accelerating rotarod task were determined in groups of naive mice. Dizocilpine in doses as low as 0.3 mg/kg produced a decreased ability to remain on the rotarod, whereas ADCI up to 30 mg/kg did not affect rotarod performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Comparative effects of arginine vasopressin, [pGlu4,Cyt6]arginine vasopressin-(4-9) and nerve growth factor on maintenance of functional tolerance to ethanol in mice.

Previous work has demonstrated that arginine vasopressin (AVP), acting in the CNS, can maintain functional tolerance to ethanol. We now show that the AVP metabolite peptide, [pGlu4,Cyt6]arginine vasopressin-(4-9), also maintains ethanol tolerance, with a potency similar to that of arginine vasopressin, while nerve growth factor has only a marginal effect. The effects of these peptides on ethanol tolerance correlate with their previously described ability to induce expression of the proto-oncogene, c-fos, in the septum, a putative mechanism underlying peptide effects on neuroadaptive processes.

Animals↗
PubMed1991

Brain regional specificity and time-course of changes in the NMDA receptor-ionophore complex during ethanol withdrawal.

Previous work, using membrane receptor binding techniques, demonstrated an increase in hippocampal MK-801 binding sites in mice after chronic ethanol ingestion. The current studies, using quantitative autoradiography, demonstrate that chronic ethanol ingestion also produces increases in MK-801 binding in cerebral cortex, striatum and thalamus, as well as in hippocampus. The persistence of changes in MK-801 binding paralleled the time-course for ethanol withdrawal seizure susceptibility. These results support the hypothesis that an increase in the number of NMDA receptor/channel complexes in hippocampus, and possibly other brain regions, plays a role in the generation or expression of ethanol withdrawal seizures.

Animals↗
PubMed1991

Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120.

Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-[1-14C] glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection.

Analysis of Variance↗
PubMed1991

Ethanol fails to modify [3H]GR65630 binding to 5-HT3 receptors in NCB-20 cells and in rat cerebral membranes.

Low concentrations of ethanol have been found to enhance the electrophysiologic effect of serotonin (5-HT) acting at 5-HT3 receptors on NCB-20 cells. To determine whether this action of ethanol reflects a change in the agonist-receptor interaction, the effect of ethanol (100 mM) on agonist and antagonist binding to 5-HT3 receptor was studied in vitro in membrane from NCB-20 cells and from cortex plus hippocampus of rat. The antagonist [3H]GR65630 was used to label 5-HT3 recognition sites. Ethanol did not change the characteristics of saturable [3H]GR65630 binding in either membrane preparation. In competition studies, the agonists 5-HT and 2-methyl-5-HT completely inhibited the binding of [3H]GR65630 to NCB-20 cell membranes, while in brain membranes the maximum displacement of specific [3H]GR65630 binding by 5-HT was approximately 30%. Ethanol decreased the affinity of the receptor for 2-methyl-5-HT, but not to 5-HT in NCB-20 cells, and had no effect on agonist binding in brain membranes. The results indicate that enhancement of 5-HT responses at 5-HT3 receptors by ethanol is not a result of changes in the equilibrium binding characteristics of the agonist.

Animals↗