Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol inhibits adenosine uptake, thereby increasing the concentration of extracellular adenosine. Elevation of extracellular adenosine increases intracellular cAMP concentration via activation of adenosine A2 receptors. Extracellular adenosine is also required for the subsequent development of ethanol-induced heterologous desensitization. Here we report that activation of cAMP-dependent protein kinase is necessary for inhibition of adenosine uptake by ethanol and for the consequent accumulation of extracellular adenosine. Ethanol does not inhibit adenosine uptake in mutants of the S49 cell line that lack receptor-stimulated cAMP production (unc cells) or cAMP-dependent protein kinase activity (kin- cells). Forskolin, which bypasses the receptor-coupling defect in unc cells to increase cAMP levels, restores inhibition of adenosine uptake by ethanol. In contrast, in kin- cells forskolin did not restore inhibition of adenosine uptake by ethanol, despite similar increases in cAMP levels. Taken together, these results suggest that cAMP-dependent protein kinase phosphorylates a component of the nucleoside transporter, thereby regulating the sensitivity of adenosine transport to ethanol.
Mol Pharmacol 1991 Nov
PMID:cAMP-dependent protein kinase regulates inhibition of adenosine transport by ethanol. 165 11

Delta-sleep-inducing peptide (DSIP) is an endogenous substance that regulates the response of the organism to stress. It was found that DSIP, like diazepam and ethanol, activates muscimol-stimulated 36Cl- uptake in the rat brain cortex and partially counteracts the stimulatory action of ethanol on this process. The effect of peptide disappears at the lowering of the incubation temperature. We propose that DSIP is a concordant regulator partly mediating its action through the membrane phospholipids.
Mol Chem Neuropathol 1991 Dec
PMID:Effect of ethanol and DSIP on the 36Cl-flux in synaptosomal vesicles. 166 53

The 987P fimbrial gene cluster has been previously cloned as a 12 kb fragment from prototype strain 987. Gene products encoded by the whole clone were analysed by utilizing an in vivo system based on the induction of transcription by T7 RNA polymerase. The sensitivity of this technique permitted us to identify new proteins involved in 987P fimbriation. In total, eight proteins were detected, their genes (fasA to fasH) were mapped and their orientation of transcription determined. Several of the gene products demonstrated typical properties of exported proteins. Precursor and processed forms could be correlated after inhibiting protein transport with ethanol. The detection of enzymatically active fusion proteins after TnphoA (Tn5IS50L::phoA) mutagenesis supported and complemented these results. One protein encoded by the 12kb fragment was found not to be related to fimbriation but rather the product of the STla gene, identified as a component of a Tn1681-like transposon.
Mol Microbiol 1991 Jan
PMID:987P fimbrial gene identification and protein characterization by T7 RNA polymerase-induced transcription and TnphoA mutagenesis. 167 18

Primary cultured sensory neurons prepared from adult mice were maintained for 8 days in vitro. Such cultures were exposed to either a range of ethanol concentrations (50-300 mM) or acetaldehyde (0.5-2 mM) in serum-free medium for up to 24 h. Treated neuronal cultures, together with untreated controls in both the presence and absence of serum, were prepared for transmission electron microscopy. Nuclear morphology was not changed following treatment with either substance at the doses studied. A number of changes were observed, however, in the cytoplasm of neurons, and these were intensified by an increase in concentration and the length of exposure. Acetaldehyde induced effects at a much lower concentration than was required to induce a response with ethanol. Myelin lamellae loosely wound around dense granular core material appeared in multivesicular bodies at low doses. The prevalence of these increased with concentrations of 100 mM ethanol and 1 mM acetaldehyde; the numbers of lamellae in each myelin figure also increased but the core material was less prominent. Electron-dense bodies were also evident at higher dosages together with evidence of vacuolation of the endoplasmic reticulum and Golgi complexes. Mitochondrial profiles similar to those in untreated neurons persisted throughout the exposure periods. The generation of these inclusions may reflect a mechanism of membrane turnover, both of internal systems and cell membrane cycling, as a response to alcohol and aldehyde treatment.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Cytoplasmic changes in primary cultured adult mouse sensory neurons induced by ethanol and acetaldehyde treatments. 168 82

Ethanol has been shown to inhibit N-methyl-D-aspartate (NMDA)-stimulated calcium influx into cerebellar granule cells grown in culture. Because NMDA-mediated responses are modulated by a number of substances, we investigated the effects of several of these agents on ethanol-induced inhibition of calcium flux. Ethanol (50 mM) inhibited NMDA-dependent Ca2+ influx by approximately 50%. The percentage of inhibition remained constant with increasing NMDA concentrations (5-250 microM). Increasing Mg2+ concentrations in the assay medium inhibited NMDA-stimulated calcium influx but the EC50 for Mg2+ was unchanged in the presence of ethanol. Glycine at concentrations of 0.3-100 microM potentiated the effects of NMDA. Glycine at concentrations in excess of 10 microM decreased ethanol-mediated inhibition of NMDA-stimulated calcium influx. D-Serine was shown to have effects similar to those of glycine, whereas L-serine was significantly less active in potentiating NMDA-stimulated activity and reversing the ethanol-induced inhibition of calcium influx. N-Methylglycine and L-leucine were ineffective in potentiating NMDA actions but high concentrations (1 mM) of N-methylglycine attenuated ethanol-induced inhibition, whereas L-leucine (1 mM) had no effect. High concentrations of N-methylglycine were shown to reduce glycine-induced enhancement at the NMDA receptor, whereas L-leucine did not affect the glycine response. Glycine did not affect kainate-stimulated calcium influx and did not alter the small amount of inhibition produced by ethanol in the response of the cells to kainate. The results demonstrate that the in vivo actions of ethanol on the NMDA systems of brain may be dependent on glycine concentrations at these receptor sites.
Mol Pharmacol 1990 Dec
PMID:Glycine site-directed agonists reverse the actions of ethanol at the N-methyl-D-aspartate receptor. 170 Dec 11

Ethanol administration to rats by ethanol vapor inhalation (14 days) results in a 40-50% reduction in the level of gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit mRNAs [4.4 and 4.8 kilobases (kb)] in the cerebral cortex. The level of alpha 2 subunit mRNA (8.0 kb) was also reduced by 29%, whereas there was no effect of prolonged ethanol exposure on the level of alpha 3 subunit mRNA (3.1 kb). Ethanol exposure did not alter the steady state levels of cerebral cortical glutamic acid decarboxylase or beta-actin mRNAs. Moreover, no alterations in the levels of total RNA, poly(A)+ RNA, or rRNA were observed, suggesting that the ethanol-induced reductions in GABAA receptor alpha 1 and alpha 2 subunit mRNAs were not the result of a generalized effect of ethanol administration on transcription or mRNA turnover. These ethanol-induced reductions in GABAA receptor alpha subunit mRNAs may underlie alterations in GABAA receptor function or number observed following prolonged ethanol exposure in rats.
Mol Pharmacol 1991 Feb
PMID:Prolonged ethanol inhalation decreases gamma-aminobutyric acidA receptor alpha subunit mRNAs in the rat cerebral cortex. 170

At nicotinic acetylcholine receptors, short chain n-alcohols (alkanols) have excitatory actions, whereas long chain alkanols inhibit channel activity. This study tests a previously proposed unitary hypothesis that suggests that these contrasting actions can be accounted for by interaction at just one hydrophobic site within the ion channel lumen. All alkanols bind to this site, but only long chain alkanols are large enough to completely block the channel. Short chain alkanols are too small to cause any channel occlusion, and in binding to the site they stabilize the open state of the receptor and enhance ion flux. In this study, we assay integrated agonist-stimulated ion efflux over 15 msec, as a measure of receptor activity. In nicotinic acetylcholine receptor-rich membrane vesicles from Torpedo, we show that, in contradiction to this elegant model, long chain and short chain alkanols appear to act at different sites. Firstly, ethanol and octanol do not compete for a single site on the receptor. Secondly, alkanol chain length dependencies for inhibition and for flux enhancement are significantly different. Thirdly, intermediate length alkanols do not partially inhibit channels, as required by the model; high concentrations of these alkanols completely inhibit the response. Fourthly, careful measurements, including determination of the free alkanol concentration, of inhibitory potencies of alkanols from propanol to decanol show no evidence for a steric contribution to the ability of an alkanol to inhibit the ion channel. Furthermore, our results suggest that the inhibitory effect of long chain alkanols may be mediated by a discrete site on nicotinic acetylcholine receptors, whereas there is no evidence that a protein site is involved in the excitatory mechanism of short chain alkanols. Indeed, it seems more likely that short chain alkanols may have a nonspecific site of action.
Mol Pharmacol 1991 Mar
PMID:Short chain and long chain alkanols have different sites of action on nicotinic acetylcholine receptor channels from Torpedo. 170 69

Mitogillin is a ribonuclease secreted by the fungus Aspergillus restrictus. The substrate for mitogillin is a short, universally conserved, sequence in ribosomal RNA. Cleavage of this sequence inactivates protein synthesis. Mitogillin was crystallized by a two-chamber vapor/liquid diffusion method using ethanol as the precipitant. This method has wider potential in the use of volatile organic solvents as precipitants. Crystals of mitogillin diffract X-rays to lattice d-spacings of at least 1.6 A, and belong to the monoclinic space group P2(1), with a = 50.4 A, b = 82.4 A, c = 38.2 A and beta = 99.8 degrees.
J Mol Biol 1991 Apr 05
PMID:Crystallization and preliminary characterization of mitogillin, a ribosomal ribonuclease from Aspergillus restrictus. 170 77

We describe a new Escherichia coli operon, the phage shock protein (psp) operon, which is induced in response to heat, ethanol, osmotic shock and infection by filamentous bacteriophages. The operon includes at least four genes: pspA, B, C and E. PspA associates with the inner membrane and has the heptad repeats characteristic of proteins that can form coiled coils. The operon encodes a factor that activates psp expression, and deletion analyses indicate that this protein is PspC; PspC is predicted to possess a leucine zipper, a motif present in many eukaryotic transcription factors. The pspE gene is expressed in response to stress as part of the operon, but is also transcribed from its own promoter under normal conditions. In vitro studies suggest that PspA and C are modified in vivo. Expression of the psp genes does not require the heat shock sigma factor, sigma32. The increased duration of psp induction in a sigma32 mutant suggests that a product (or products) of the heat shock response down-regulates expression of the operon.
J Mol Biol 1991 Jul 05
PMID:Characterization and sequence of the Escherichia coli stress-induced psp operon. 171 97

Recent studies indicate that ethanol (EtOH) potentiates ion current through the channel associated with the 5-hydroxytryptamine3 (5-HT3)-type serotonin receptor. The present study was designed to determine 1) whether such potentiation occurs in adult mammalian neurons expressing 5-HT3 receptors; 2) whether potentiation is selective for the 5-HT3 receptor, relative to other ligand-gated ion channels; and 3) possible mechanisms by which EtOH potentiates this response. EtOH potentiated 5-HT3 receptor-mediated ion current in freshly isolated nodose ganglion neurons at concentrations similar to those previously reported to be effective in neuroblastoma cells (25-100 mM). Current was blocked by the selective 5-HT3 antagonist ICS 205-930 even in the presence of EtOH, and current activated by a 5-HT3 agonist (2-methyl-5-HT) was potentiated by EtOH. Thus, EtOH appears to produce potentiation via an alteration in the function of 5-HT3 receptors and not through an independent effect. gamma-Aminobutyric acidA receptor-mediated Cl- current was not potentiated by EtOH in neurons in which potentiation of responses to 5-HT was observed. Methanol potentiated 5-HT3 receptor-mediated current with a potency lower than that of EtOH. Potentiation by EtOH decreased with increasing 5-HT concentration. In addition, EtOH increased the decay rate of current. EtOH did not alter the reversal potential of the 5-HT3 receptor-mediated current. These observations indicate that intoxicating concentrations of EtOH selectively potentiate 5-HT3 receptor-mediated responses by increasing the apparent potency of 5-HT for activating ion current.
Mol Pharmacol 1991 Aug
PMID:Ethanol potentiation of 5-hydroxytryptamine3 receptor-mediated ion current in neuroblastoma cells and isolated adult mammalian neurons. 171 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>