Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ethanol on GTP-binding protein of cortical adenylate cyclase (AC) system in the Wistar and Fischer 344 rats was examined. In both Wistar and Fischer 344 rats, ethanol (100mM) potentiated Gpp (NH) p-stimulated AC activity and decreased EC50 for Gpp (NH)p in the cerebral cortical membrane (CCM). Ethanol treatment also augmented Mn-stimulated AC activity in Wistar CCM, whereas there was no significant change in Fischer 344 CCM. IC50 calculated from the Gpp (NH)p (0.01-0.3 microM) inhibition of forskolin-stimulated AC was decreased by ethanol treatment in Wistar CCM, but this was not the case in Fischer 344 CCM. There was no appreciable change in ADP-ribosylation of Gs and Gi in CCM with pertussis or cholera toxin. These results suggest that ethanol in vitro enhances the Gi function as well as affecting the Gs function in Wistar rat cortical AC system, and the effect of ethanol on Gi protein are different in Wistar and Fischer 344 CCM.
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PMID:[Effects of ethanol on GTP binding protein function in rat cerebral cortex: strain difference between Wistar and Fischer 344 rats]. 212 Nov 24

The interaction of ethanol with GABAB-receptor system and the selectivity of phaclofen for GABA-receptor subtypes were investigated by employing an in vitro model of 36Cl-influx assay in mammalian cultured neurons and also in vivo models of picrotoxin- and NMDA-induced convulsions in rats. Ethanol (20 mM), without having any effect per se, potentiated the effect of GABA on 36Cl-influx, whereas at concentration 50 mM, ethanol activated Cl(-)-channels directly in mice spinal cord cultured neurons. In contrast, (-)baclofen (100 microM) did not modify the effects of GABA or ethanol on 36Cl-influx. Similarly, phaclofen (500 microM), as well as pertussis toxin (140 ng/ml, overnight incubation) did not modify these effects. Interestingly, phaclofen (200 micrograms i.c.v.) reversed the anticonvulsant effect of ethanol, but not that of pentobarbital or diazepam or progabide, against picrotoxin-induced convulsions in rats. However, phaclofen failed to modify the anticonvulsant effect of ethanol against NMDA-induced convulsions. These observations indicate that phaclofen is devoid of GABAA-receptor blockade property, and the anticonvulsant effect of ethanol against picrotoxin may be mediated through the activation of both GABA-receptor subtypes.
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PMID:Are GABAB receptors involved in the pharmacological effects of ethanol? 217 47

The effects of ethanol on the beta adrenergic receptor-coupled adenylate cyclase system were examined in vitro using membranes prepared from S49 lymphoma cells. Ethanol caused a dose-dependent increase in adenylate cyclase activity in membranes prepared from wild-type cells when the activity was measured in the presence of GTP. Activity measured in the presence of isoproterenol was also increased by ethanol, but the fold-stimulation by isoproterenol was lower in the presence of ethanol. Ethanol also shifted the dose-response curve for stimulation of the enzyme by isoproterenol to the right. This shift was due to a decrease in the affinity of the beta adrenergic receptor for isoproterenol. A decrease in the affinity of the receptor for the antagonists [125I]iodopindolol and propranolol was also observed, but the magnitude of this effect was less than that seen with the agonist isoproterenol. The density of binding sites for [125I]iodopindolol was not affected by ethanol. Dose-response curves for NaF and guanosine-5'-O-(3-thiotriphosphate), both of which stimulate adenylate cyclase activity through an effect on the stimulatory guanine nucleotide-binding protein (Gs), were shifted to the left by the addition of ethanol. In membranes prepared from the CYC- variant of S49 cells, which lacks the alpha subunit of Gs, guanosine-5'-O-(3-thiotriphosphate) inhibited forskolin-stimulated adenylate cyclase activity. The inhibition by guanosine-5'-O-(3-thiotriphosphate) was not affected by ethanol. In membranes prepared from both wild-type and CYC- S49 cells, ethanol inhibited forskolin-stimulated adenylate cyclase activity. Whereas the inhibition of this activity by GTP was greatly attenuated in membranes prepared from CYC- S49 cells which had been pretreated with pertussis toxin, the inhibition by ethanol was not affected by pretreatment with pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ethanol in vitro on the beta adrenergic receptor-coupled adenylate cyclase system. 284 25

Modulation of alpha 2-adrenergic and opioid neurotransmission may contribute to ethanol intoxication, tolerance, and physical dependence. We showed previously that ethanol increased the expression of functional delta-opioid receptors in NG108-15 cells (Charness, M. E., Querimit, L. A., and Diamond, I. (1986) J. Biol. Chem. 261, 3164-3169). Here we report that long-term (2 days) treatment of NG108-15 cells with ethanol increased the binding of the alpha 2-adrenergic receptor (alpha 2AR) antagonist [3H]rauwolscine and the muscarinic acetylcholine receptor (mAChR) antagonist [3H]quinuclidinyl benzilate by 2.8- and 1.4-fold, respectively. Increased receptor expression was associated with a proportionate increase in the potency of oxymetazoline and carbachol in inhibiting cAMP accumulation. Ethanol did not change the expression of G alpha i2 and reduced levels of G alpha s. Pertussis toxin pretreatment did not prevent the ethanol-induced increase in alpha 2AR, mAChR, and delta-opioid receptor expression. Ethanol caused a large (3.6-fold), dose-dependent increase in the abundance of alpha 2BAR mRNA (rat cDNA probe RNG, 4.1-kb transcript). Ethanol-induced increases in alpha 2BAR and alpha 2CAR (rat probe RG10, 2.5-kb transcript) mRNAs were first detected after 6 h of exposure to 100 mM ethanol, became maximal after 24 h, and persisted for up to 5 days. In contrast, ethanol caused only a small (1.3-fold) increase in the abundance of hm4 mAChR mRNA and did not change levels of G alpha i2 and G alpha s mRNAs. Our data indicate that clinically attainable concentrations of ethanol regulate alpha 2AR gene expression within the time frame of a single session of drinking.
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PMID:Ethanol differentially increases alpha 2-adrenergic and muscarinic acetylcholine receptor gene expression in NG108-15 cells. 822 69

Resident peritoneal macrophages synthesized and released eicosanoids when challenged by zymosan, a phagocytosable particle. Incubation of these cells with ethanol resulted in dose-dependent inhibition of arachidonic acid release and eicosanoid generation in response to zymosan. Ethanol affected the extent but not the ratio of eicosanoids released. When assayed in a cell-free system, endogenous phospholipase A2 activity was neither affected by the presence of ethanol in the incubation medium nor by preincubation of the cells with ethanol. Ethanol also inhibited arachidonic acid release in response to phorbol myristate acetate, a compound that, like zymosan, triggered a pertussis-toxin-sensitive response. When cells that had been previously treated with pertussis toxin were used, no further inhibitory effect of ethanol was seen in response to both zymosan and phorbol myristate acetate. On the other hand, ethanol had no effect on arachidonic acid release stimulated by ionophore A23187 or lipopolysaccharide, two compounds that triggered a pertussis-toxin-insensitive response. Moreover, ethanol was able to nearly abolish arachidonic acid release in response to fluoroaluminate, a direct activator of G-proteins. Altogether, the results of this study suggest that ethanol inhibits zymosan-stimulated eicosanoid production by interacting with a G-protein--or a G-protein-mediated process--that is critically involved in arachidonic acid mobilization.
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PMID:Ethanol inhibits zymosan-stimulated eicosanoid production in mouse peritoneal macrophages. 828 Jul 70

The possibility that a 7-day period of ethanol exposure could regulate expression of specific GTP-binding regulatory proteins was investigated in two distinct brain regions from two different lines of ethanol-sensitive mice. Following ethanol treatment, plasma membranes were prepared from cerebellum and pons of short and long sleep mice. Studies of membranes were performed to assess hormone-sensitive adenylylcyclase activity and to quantify expression of G-protein subunits. Immunoblot analysis showed that levels of Gi alpha(1) and Gi alpha(2) were markedly increased in cerebellar and pons membranes from ethanol-exposed mice compared to controls. Treatment of short sleep mice with ethanol enhanced ADP-ribosylation of both a 41- and a 39-40 kDa protein catalyzed by pertussis toxin. Ethanol did not alter expression of Gs alpha as assessed by immunoblot analysis, cholera toxin-dependent ADP-ribosylation, or by the ability of detergent extracted Gs alpha to reconstitute a functional adenylylcyclase in membranes from S49 cyc- murine lymphoma cells, a cell line which genetically lacks Gs alpha. Moreover, ethanol exposure did not influence levels of G(o) alpha or G beta 35-36 in either cerebellar or pons membranes. Cerebellar and pons membranes from ethanol-exposed short sleep mice demonstrated significantly less adenylylcyclase activity following stimulation with GTP, GTP gamma S, AlF, forskolin, and stimulatory ligands for three distinct receptors which couple to Gs alpha. Pretreatment of membranes with pertussis toxin reversed the ethanol-induced inhibition in adenylylcyclase activity. These observations were not limited to one line of mice but were also documented in a second line of ethanol-sensitive mice (e.g. long sleep). We conclude that ethanol exposure enhances expression of Gi alpha(1) and Gi alpha(2) in ethanol-sensitive mice, and is associated with decreased adenylylcyclase activity. Enhanced expression of Gi alpha(1) and Gi alpha(2) may contribute to impaired signal transduction in the central nervous system, and reduce the efficacy of neurotransmitters which signal through the adenylylcyclase system.
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PMID:Chronic ethanol treatment increases expression of inhibitory G-proteins and reduces adenylylcyclase activity in the central nervous system of two lines of ethanol-sensitive mice. 842 35

Ethanol modulates agonist responses in liver cells, which are the major site of ethanol metabolism. Mitogen-activated protein kinases (MAPKs) are involved in the integration of multiple signaling pathways leading to cellular responses. However, the effect of ethanol on liver MAPK is not known. To this end, we studied the activation of MAPK in a normal mouse embryonic liver cell line (BNLCL2) after acute and chronic exposure to ethanol. Acute exposure to ethanol (0-400 mM) for 1 hr had no effect on either basal or serum- and phorbol-12-myristate-13-acetate (PMA)-stimulated MAPK activity. Chronic exposure to ethanol (0-400 mM) for 24 hr potentiated the stimulation of MAPK by serum, PMA, or thrombin. Maximum potentiation was observed with 200 mM ethanol (2- to 3-fold higher than control cells). Chronic exposure had no significant effect on epidermal growth factor-stimulated MAPK activity. In-gel MAPK assay of cytosolic extracts and of immunoprecipitates obtained with MAPK antibody demonstrated that ethanol potentiated the activation of both p42 and p44 MAPKs. When cells were pretreated with pertussis toxin, the potentiation by ethanol was abolished. It is concluded that ethanol potentiates MAPK in fetal liver cells by a pertussis toxin-sensitive G-protein-dependent mechanism.
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PMID:Potentiation of mitogen-activated protein kinase by ethanol in embryonic liver cells. 861 3

Effects of ethanol on signal transduction in neuronal membranes are supposed to occur by the interaction with heterotrimeric guanine nucleotide-binding proteins (G-proteins). Several substances affect signal transduction by activation of G-proteins directly independent of receptors. We show that similar to those substances, ethanol stimulates high-affinity guanosine triphosphate (GTP)-hydrolysis in SH-SY5Y membranes at concentrations of 50 mM and higher in a pertussis toxin-sensitive manner. Compared with ethanol at a concentration of 170 mM, other alcohols were without or with respect to methanol with a slight effect on high-affinity GTP-hydrolysis in SH-SY5Y membranes. Ethanol also stimulates the GTPase of the purified G-protein transducin. The findings suggest that ethanol affects signal transduction in neuronal membranes by direct activation of pertussis toxin-sensitive G-proteins.
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PMID:Activation of pertussis toxin-sensitive G-proteins in membranes of SH-SY5Y human neuroblastoma cells and bovine transducin by ethanol. 884 4

The possible modulation and of co-modulation by the cerebellar GABAB and adenosine A1 receptors of ethanol-induced motor impairment were investigated in the mice using rotorod performance as the test response. Direct cerebellar microinfusion of GABAB agonist, baclofen, and antagonist, phaclofen, into the permanently cannulated mice, produced a dose-dependent accentuation and attenuation, respectively of ethanol-induced motor impairment. The baclofen and phaclofen exhibited accentuation and attenuation, respectively, via GABAB receptors linked to pertussis toxin-sensitive G protein. A comodulation by the cerebellar adenosine A1 receptors was also observed because intracerebellar microinfusion of adenosine agonists NB-cyclohexyladenosine (CHA), 5'-N-ethylcarbox-amidoadenosine (NECA), and 2-p-(2-carboxyethyl)-phenyl-ethylamino-5'-N-ethylacarbox- amidoadenosine (CGS-21680), and antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX), also accentuated and attenuated, respectively, ethanol-induced motor impairment. The accentuation of ethanol-induced motor impairment by baclofen was further enhanced after the intracerebellar microinfusion of CHA, suggesting a co-modulation by the co-localized adenosine A1 receptors. A similar response was observed after the intracerebellar microinfusion of adenosine A1 = A2 agonist NECA and the several-fold higher dose of adenosine A2-selective agonist CGS-21680. Ethanol-induced motor impairment was markedly blocked by intracerebellar A1-selective antagonist, DPCPX, as well as by the intracerebellar pertussis toxin pretreatment suggesting again a co-modulation by the adenosine A1 receptors and the involvement of pertussis toxsin-sensitive G protein, respectively. The almost 25-fold higher dose of CGS-21680 to accentuate and DPCPX to attenuate, respectively, ethanol-induced motor impairment together with the reported cerebellar localization of adenosine A1 subtype only, suggested A1 receptor activation by NECA and CGS-21680. The functional similarity between GABAB and adenosine A1, receptors associated with their anatomical co-localization on the cerebellar granule cells, mainly axons and axonal terminals, may suggest a possible common adenylate cyclase catalytic unit as the basis of modulation of ethanol's motor impairment by these two receptor mechanisms.
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PMID:Mouse cerebellar GABAB participation in the expression of acute ethanol-induced ataxia and in its modulation by the cerebellar adenosinergic A1 system. 888 16

Ethanol (1-200 mM), a potent depressor of respiration and motor activity, potentiated the inhibitory Cl- current activated by glycine in 80% of the cultured mouse spinal (n = 236) neurons studied. Ethanol (100 mM) had no effect on the gamma-aminobutyric acidA current and slightly inhibited the N-methyl-D-aspartate current in these neurons. Ethanol increased the affinity of the receptors to glycine without changing the maximal amplitude of the glycine current. The EC50 was reduced from 54 +/- 3 microM in the absence of ethanol to 38 +/- 5 microM in the presence of ethanol. Activation of GTP binding proteins in the neurons with intracellular guanosine-5'-0-(2-thiotriiphosphate) (0.5 mM) enhanced the effect of ethanol, and application of a similar concentration of guanosine 5'-0-(2-thiodiphosphate had an inhibitory effect upon the current potentiation. The potentiating effect of ethanol persisted after culturing the neurons with pertussis toxin, but not with cholera toxin, an irreversible activator of Gs. Activation of cyclic AMP-dependent protein kinase by cyclic AMP and Sp-adenosine-3',5'-cyclic monophosphothioate triethylamine salt, but not of protein kinase C and protein kinase G, potentiated the glycine current. The effect of Sp-adenosine-3',5'-cyclic monophosphothioate triethylamine salt, but not of ethanol, was inhibited completely by the protein kinase A peptide inhibitor. These results suggest that ethanol potentiates the glycine activated Cl- current by modifying a signal transduction step other than protein kinase A.
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PMID:Potentiation of the glycine-activated Cl- current by ethanol in cultured mouse spinal neurons. 896 32


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