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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We ascertained that transient exposure to ethanol, above 18%, was deletionogenic to an Escherichia coli strain with a fragment (12.5 kb) of bacteriophage lambda integrated within the chromosome. The lambda attL B.P' through P fragment provided a forward selection for mutants, and a target for mutagenesis. The cells were killed by thermal derepression of transcription and replication of the lambda fragment when transferred from 30 degrees to 42 degrees C. Survivor mutants, capable of forming colonies at 42 degrees C, were selected from untreated starting cells. About half no longer supported marker rescue of the lambda fragment imm lambda (immunity) region, comprising the cI repressor, and the PL and PR promoters. Ethanol treatment of starting cells increased the occurrence of imm lambda-defective clones to near 100%. The mutations responsible for the imm lambda defect were found to be large deletions (12 kb or more of DNA). Ethanol treatment of the starting cells also produced a 5- to 18-fold increase in the occurrence of E. coli pgl mutations, which likely arose by the deletion mechanism generating the imm lambda defects, since pgl was closely linked to the integrated lambda fragment. A unifying hypothesis for these observations was that ethanol was deletionogenic. The inclusion or substitution of the int-kil segment of the lambda fragment produced no real change in the spontaneous occurrence of large imm lambda deletions from the untreated cells. Substitution of this segment suppressed the deletionogenic effect of ethanol, implying a prerequisite for sequence homology or gene function from this interval.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Gen Genet 1990 Jun
PMID:Alcohol treatment of defective lambda lysogens is deletionogenic. 214 86

Chronic exposure to ethanol results in heterologous desensitization of receptors coupled to adenylyl cyclase via Gs, the stimulatory guanine nucleotide regulatory protein. Ethanol-induced accumulation of extracellular adenosine is required for the development of heterologous desensitization (Nagy, L. E., Diamond, I., Collier, K., Lopez, L., Ullman, B., and Gordon, A. S., Mol. Pharmacol., in press). To understand the mechanism underlying ethanol-induced increases in extracellular adenosine, we examined the interaction of ethanol with the adenosine transport system in S49 lymphoma cells. We found that ethanol inhibited nucleoside uptake without affecting deoxyglucose or isoleucine transport. Inhibition of adenosine uptake was due to decreased influx via the nucleoside transporter. Thus, ethanol-induced increases in extracellular adenosine appear to be due to inhibition of adenosine influx. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol, i.e. ethanol no longer inhibited uptake. Consequently, ethanol no longer increased extracellular adenosine concentrations. Taken together with our previous studies, these results suggest that ethanol inhibition of adenosine influx leads to an increase in extracellular adenosine which causes an initial increase in intracellular cAMP levels and subsequent development of heterologous desensitization of cAMP signal transduction.
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PMID:Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter. 229 33

Ethanol increases the uptake of 45Ca by isolated baby hamster kidney (BHK) cells in vitro. The effect is dependent on ethanol and 45Ca++ concentration and on the incubation time. Fructose-1,6-diphosphate (FDP) added at different concentration during the pre-incubation exerts a protective effect through a membrane-stabilizing action which is consistent with its in vivo anti-alcohol activity documented in previous studies.
Mol Cell Biochem 1990 Jun 01
PMID:Fructose-1,6-diphosphate counteracts ethanol-stimulated calcium uptake in isolated BHK cells. 236 53

To further define the sarcolemmal effects of ethanol and acetaldehyde, their effects on Na pump function were studied in synchronously contracting monolayers of neonatal rat myocardial cells. The effects of ethanol (10 mg/dl to 1000 mg/dl: 2 X 10(-3) M-0.2 M) and acetaldehyde (10(-6) M to 10(-4) M) on total 42K influx, ouabain-sensitive 42K influx, Na pump density (from specific 3H-ouabain binding) and pump turnover rates were measured. Applied acutely ethanol had no effect on 42K influx but after 30 min of treatment 42K influx was decreased by 13%, 23% and 48% in 100 mg/dl, 300 mg/dl and 1000 mg/dl ethanol respectively. This primarily reflected a decrease in mean ouabain-sensitive K+ influx from a control of 12.54 to 9.90, 8.95 and 6.68 (p-mol/cm2/s) in 100, 300 and 1000 mg/dl (2 X 10(-2) M, 6 X 10(-2) M) ethanol. Acetaldehyde in the concentrations tested had no effect on K+ influx. Ethanol treatment produced a decrease in Na pump density, maximum within 30 min and dose-dependent, at concentrations of 100 mg/dl (22%), 300 mg/dl (37%) and 1000 mg/dl (55%). Acetaldehyde had no effect on Na pump density. In the presence of ethanol (300 mg/dl and 1000 mg/dl) intracellular Na+ increased significantly and the Na+ efflux declined in parallel with the K+ influx. From the ouabain-sensitive K+ and Na+ fluxes and the Na pump density individual pump turnover rates were calculated at 62.5/s in control cells and 66/s and 84/s in cells treated with 300 mg/dl (6 X 10(-2) M) and 1000 mg/dl (0.2 M) respectively. We conclude that ethanol, but not acetaldehyde has a depressant effect on sarcolemmal Na pump function. The results suggest this is due primarily to a decrease in the number of sarcolemmal Na pump sites.
J Mol Cell Cardiol 1987 May
PMID:The effect of ethanol and acetaldehyde on Na pump function in cultured rat heart cells. 244 97

The fluorescent Ca2+ indicator fura-2 was used to follow cytosolic Ca2+ transients during excitation-contraction coupling in suspensions of isolated rat heart cells induced to beat synchronously by electrical field stimulation. The Ca2+ transient reached a maximum at about 30 ms after application of the electrical stimulus and then relaxed to the basal level over the following 200 ms. Treatment of the myocytes with 0.25 to 2.0% ethanol (40 to 340 mM) caused a decrease in the peak of the Ca2+ transient, with no apparent change in the time to peak. This effect of ethanol occurred progressively over a period of about 1 min before a new stable state was achieved. At 1% ethanol the peak Ca2+ level was reduced by 50%. Ethanol reversed the stimulatory effect of isoproterenol on peak Ca2+ and at high levels of ethanol the beta-adrenergic agonist no longer caused any enhancement of the Ca2+ transient. Ethanol did not cause any marked change in the basal Ca2+ level between beats. The effects of ethanol were readily reversible. These results suggest that the negative inotropic effect of ethanol observed in intact cardiac muscle preparations may result in part from interference with the Ca2+ fluxes responsible for excitation-contraction coupling in ventricular myocytes.
J Mol Cell Cardiol 1989 Jun
PMID:Ethanol inhibits electrically-induced calcium transients in isolated rat cardiac myocytes. 277 7

Ethanol (0.6 g/100 g) was administered orally to rats by means of an intragastric tube. This caused an accumulation of secretory vesicles laden with VLDL particles which were seen 90 min after administration and later disappeared. Lysosomes and Golgi complex secretory vesicle (GCSV) fractions were isolated. The proteolytic and lipolytic activities of these fractions were measured in order to assess their possible role in the elimination of the initially retained secretory material. There was no change in proteolysis neither in lysosomes or in the GCSV-fraction from ethanol-intoxicated rats when measured by the release of degradation products during incubation. Similarly, the activities of acid hydrolases were unaffected by acute ethanol intoxication. On the other hand, lipolysis increased by some 50-100% in the GCSV fraction, whereas the lysosomes displayed unchanged lipolytic levels compared with controls. Ultrastructurally, the GCSV-fraction from ethanol-intoxicated rat livers showed signs of disintegrated VLDL particles. It is concluded that acute ethanol intoxication causes an increase in lipolysis but not in proteolysis in the operationally defined GCSV fraction. Since triacylglycerol lipase activities did not change in the GCSV fraction, increased amounts of substrate seem to cause the enhanced lipolysis observed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Ethanol intoxication stimulates lipolysis in isolated Golgi complex secretory vesicle fraction from rat liver. 286 46

Low concentrations of ethanol (10-100 mM), added to assays in vitro, altered agonist (isoproterenol) binding to mouse cerebral cortical beta-adrenergic receptors in a reversible manner. Ethanol decreased the affinity of the high affinity form of the receptor for isoproterenol but had no effect on the affinity of the low affinity form of the receptor, the proportion of high and low affinity forms of the receptor, the total number of agonist-binding sites, or antagonist binding. The selective effect of ethanol on the properties of the high affinity agonist-binding site suggested that ethanol alters the characteristics of the complex of the receptor and Gs, the guanine nucleotide-binding protein. In cerebral cortical membranes of mice that had ingested ethanol chronically, isoproterenol binding data were best fit by a one-site model, even in the absence of guanine nucleotides. This change, when considered together with previously reported changes in adenylate cyclase activity, is reminiscent of heterologous desensitization of the beta-adrenergic receptor. Thus, both acute and chronic ethanol administration may produce changes in adrenergic function in brain.
Mol Pharmacol 1987 Aug
PMID:Effect of ethanol on mouse cerebral cortical beta-adrenergic receptors. 288 6

Phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown was stimulated by agonists acting at muscarinic cholinergic and alpha 1-adrenergic receptors in mouse brain. Ethanol, in vitro, inhibited basal cerebral cortical PIP2 breakdown with a threshold concentration of 75-100 mM. Basal PIP2 breakdown in hippocampus and striatum was less sensitive to ethanol. A high concentration of ethanol (500 mM) increased the EC50 for carbachol stimulation of PIP2 breakdown in all three brain areas, but had no effect on the EC50 for norepinephrine. Following chronic ingestion of ethanol by mice, the EC50 for carbachol stimulation of PIP2 breakdown in cortex was decreased, and there was no change in striatum. These effects were consistent with previously observed increases in quinuclidinylbenzilate (QNB) binding in cortex, but not striatum, of mice fed ethanol chronically. However, in hippocampus, where chronic ethanol ingestion had also induced an increase in QNB binding, the EC50 for carbachol stimulation of PIP2 breakdown was increased. Binding studies using the specific M1 muscarinic cholinergic receptor antagonist, pirenzepine, revealed that the number of pirenzepine-binding sites was increased in cortex, but not hippocampus (or striatum) of ethanol-fed mice. These results support the hypothesis that high affinity pirenzepine-binding sites are coupled to PIP2 breakdown in mouse cortex. The changes in cerebral cortex represent one of the first demonstrations of a functional correlate of a change in receptor density in ethanol-treated animals. Increased sensitivity to cholinergic agonists in cortex may contribute to particular signs of ethanol withdrawal.
Mol Pharmacol 1986 Jul
PMID:Acute and chronic effects of ethanol on receptor-mediated phosphatidylinositol 4,5-bisphosphate breakdown in mouse brain. 301 7

Rates of NADPH generation by the pentose phosphate pathway were evaluated in perfused livers from ethanol-fed or control rats by measuring the production of 14CO2 from 1-14C-glucose. Under basal perfusion conditions, livers from ethanol-fed rats released lactate and pyruvate into the perfusate at rates that were only 19% of the control values. Under these conditions, calculated rates of NADPH generation by the pentose cycle in livers of the ethanol-fed rats were only 50% of rates obtained with livers of control rats. 7-Ethoxycoumarin (7-EC), a substrate for mixed function oxidation, was infused to increase rates of hepatic NADPH utilization. In livers from control rats, 7-EC was oxidized at a rate of 2.6 mumol/g/hr, but rates of NADPH generation by the pentose cycle were increased by 8.8 mumol/g/hr. In livers from ethanol-fed rats, 7-EC was metabolized at rates of 7.2 mumol/g/hr, but the generation of NADPH by the pentose cycle was increased by only 3.9 mumol/g/hr. The infusion of 7-EC was associated with increases in rates of O2 uptake that exceeded rates of mixed function oxidation in both groups of animals. Ethanol feeding decreased the activity of glucose-6-phosphate dehydrogenase by 40% and decreased the concentrations of glycogen by 66%. Thus, the decrease in pentose cycle flux in perfused livers may be due to diminished activity of the rate-controlling enzyme and/or diminished substrate supply from glycogen. However, cytosolic NADP+/NADPH ratios were identical in livers of both groups. Because NADPH was not depleted during the mixed function oxidation of 7-EC in livers from ethanol-fed rats, it is concluded that other hepatic sources of NADPH compensate for the diminished generation by the pentose cycle.
Mol Pharmacol 1987 Jun
PMID:Diminished pentose cycle flux in perfused livers of ethanol-fed rats. 360 Jun 8

The effect of ethanol on intracellular ionized calcium concentrations (Cai) was studied in synaptosomes isolated from mouse whole brain and in hepatocytes isolated from rat liver. The fluorescent calcium chelator, fura-2, was used to quantitate Cai. Incubation of synaptosomes with ethanol (350-700 mM) increased resting Cai and decreased the effectiveness of KCl to raise Cai in a concentration-dependent manner. Ethanol produced an initial rapid (less than 10 sec) increase in resting Cai that remained elevated for at least 14 min in the presence of the drug. The increase in resting Cai was correlated with the inhibitory effect of ethanol on depolarization-induced increases in Cai. Resting Cai was dependent on the external calcium concentration (0-1 mM). However, the ethanol-induced increase in resting Cai (expressed as percent of control) did not differ in the presence of several extracellular calcium concentrations (0.01, 0.1, and 1 mM). Incubation of synaptosomes in a Na-free buffer resulted in a higher resting Cai and slightly enhanced the effect of ethanol to increase resting Cai. In contrast to these results in brain tissue, ethanol (30-600 mM) did not alter resting Cai or vasopressin-stimulated increases in Cai in hepatocytes. Our results suggest that the anesthetic effects of alcohols may be mediated, in part, by increased resting Cai and by decreased calcium influx through voltage-sensitive calcium channels. In addition, our findings suggest possible mechanisms by which ethanol increases resting Cai in neuronal tissue.
Mol Pharmacol 1987 Dec
PMID:Effect of ethanol on intracellular ionized calcium concentrations in synaptosomes and hepatocytes. 369 60


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