Inhibition of enzyme induction in Pseudomonas aeruginosa by exogenous nucleotides

1978 ◽  
Vol 24 (7) ◽  
pp. 811-817 ◽  
Author(s):  
Lynda C. Kight-Olliff ◽  
J. W. Fitzgerald
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cyclic Amp ◽  
Enzyme Induction ◽  
Inhibitory Effect ◽  
Cell Suspensions ◽  
Resting Cell ◽  
Nucleoside Triphosphates ◽  
Stimulation Of

Alkylsulfatase induction in resting cell suspensions of P. aeruginosa was inhibited by exogenously supplied adenosine or by ATP (2 mM). Adenine phosphate had no effect while AMP or ADP caused a slight stimulation of induction. The inhibitory effect of ATP required the presence of added Mg2+, was not reversed by cyclic-AMP(2 mM), and was independent of the nature of the inducer. Of a number of other nucleoside triphosphates tested, only UTP (2 mM) acted as an inhibitor of induction. These nucleotides at external concentrations of 6 mM also inhibited alkylsulfatase induction in actively growing cells.

Reversal of succinate-mediated catabolite repression of alkylsulfatase in Pseudomonas aeruginosa by 2,4-dinitrophenol and by sodium malonate

1978 ◽  
Vol 24 (12) ◽  
pp. 1567-1573 ◽  
Author(s):  
J. W. Fitzgerald ◽  
L. C. Kight-Olliff ◽  
G. J. Stewart ◽  
N. F. Beauchamp
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Induction Period ◽  
Sodium Succinate ◽  
Cell Suspensions ◽  
Atp Content ◽  
Succinate Oxidation ◽  
Sodium Malonate ◽  
Atp Levels ◽  
Sodium Malate ◽  
Stimulation Of

The Kreb's cycle intermediates and related metabolites (e.g., acetate) repressed the induced synthesis of alkylsulfatase in resting cell suspensions of Pseudomonas aeruginosa. At concentrations which caused substantial repression, sodium succinate as well as sodium malate, fumarate, and α-ketoglutarate were oxidized to yield consistently high levels of ATP throughout the induction period. Sodium oxalacetate which was markedly less effective as a metabolite repressor generated high ATP levels only during the first 2 h of the induction period. The addition of 2,4-dinitrophenol or sodium malonate to cell suspensions containing the inducer (sodium hexan-1-yl sulfate) and succinate overcame repression of alkylsulfatase formation and resulted in a reduction in the ATP content to levels found in cells exposed only to inducer. An apparent stimulation of alkylsulfatase induction occurred in the absence of succinate when cells were incubated with 2,4-dinitrophenol and inducer. In this case, the ATP content of the cell suspension fell to levels substantially below those occurring as a result of inducer catabolism. Collectively, these data suggest that the effectiveness of succinate as a metabolite repressor is related to the ATP levels generated as a consequence of succinate oxidation.

scholarly journals Alteration of Platelet Cyclic AMP (cAMP) by Ethanol

1977 ◽  
Author(s):  
D.H. Cowan ◽  
M. Kikta ◽  
D. Baunach
Keyword(s):  
Cyclic Amp ◽  
Platelet Function ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Platelet Dysfunction ◽  
Camp Metabolism ◽  
Subnormal Level ◽  
Camp Levels ◽  
Stimulation Of

Studies of cAMP in human platelets exposed to ethanol were done to assess one possible mechanism for ethanol-related platelet dysfunction. Ingestion of ethanol by 3 subjects produced blood ethanol levels from 65-76 mM. Thrombocytopenia occurred in 1 subject and impaired platelet function occurred in all. Platelet cAMP decreased 36,51, and 59% below control levels. Infusion of ethanol to 2 normals produced blood ethanol levels of 43 mM and decreased platelet cAMP by 15% and 22%. Incubation of normal platelets with 86 mM ethanol in vitro decreased cAMP from 13.8 ± 2.9 (1 SD) to 9.4 ± 3.5 (p<0.02). By contrast, ethanol did not impair the increase in cAMP that occurred with 1.3 μM PGE1. Further, ethanol enhanced the increase in cAMP produced by 2.0 mM papaverine (Pap) by 160-220% and that produced by Pap + PGE1 by 58%. Dopamine, 0.1 mM, caused a 23% decrease in the basal level of cAMP, a 31% decrease below the subnormal level of cAMP seen with ethanol alone, and a 41% reduction in the increased level of cAMP produced by Pap + ethanol. The effect of ethanol on platelet cAMP metabolism is complex. Ethanol reduces basal levels of cAMP, does not decrease elevated levels that result from PGE1 stimulation of adenylate cyclase, and augments the inhibitory effect of Pap on platelet phosphodiesterase (PDE). Despite causing a decrease in basal cAMP levels, ethanol may impair platelet function by potentiating the effect of agents or other conditions which increase cAMP. The effect of ethanol on Pap-stimulated PDE activity may be blocked by dopamine, a neuropharmacologic agent that is actively accumulated by platelets.

scholarly journals Stimulation by ATP-Mg2+ and inactivation by cyclic-AMP-dependent phosphorylation of a cytosolic monkey brain aminopeptidase

1989 ◽  
Vol 258 (3) ◽  
pp. 777-783 ◽  
Author(s):  
S Ramamoorthy ◽  
A S Balasubramanian
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Aminopeptidase Activity ◽  
Serine Residue ◽  
Atpase Inhibitor ◽  
Dependent Protein Kinase ◽  
Monkey Brain ◽  
Dependent Protein ◽  
Natural Peptides ◽  
Stimulation Of

The activity of a purified cytosolic aminopeptidase (Mr 79,000) from monkey brain was stimulated about 4-fold by ATP-Mg2+. The stimulation was seen with either synthetic aminopeptidase substrates or natural peptides such as enkephalins. Both ATP and Mg2+ were required for stimulation, and ADP did not inhibit the stimulation. Non-hydrolysable analogues of ATP, deoxy-ATP and other nucleoside triphosphates stimulated to a lesser extent compared with ATP, whereas nucleoside mono- or di-phosphates were ineffective. The enzyme did not exhibit any ATPase activity. An ATPase inhibitor, orthovanadate, had no inhibitory effect on the ATP-Mg2+ stimulation. The aminopeptidase was not autophosphorylated by [gamma-32P]ATP and Mg2+, but in the presence of cyclic AMP-dependent protein kinase underwent phosphorylation on serine residue(s). Phosphorylation resulted in inactivation of the aminopeptidase activity, and also resulted in a decreased stimulation of the enzyme by ATP-Mg2+.

SUBSTRATE-DEPENDENT PHOSPHORYLATION IN RESTING CELLS OF PSEUDOMONAS AERUGINOSA

1961 ◽  
Vol 7 (1) ◽  
pp. 91-97
Author(s):  
G. A. Strasdine ◽  
J. J. R. Campbell ◽  
H. P. C. Hogenkamp ◽  
J. N. Campbell
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Electron Transport Chain ◽  
Phosphate Uptake ◽  
Growth Yield ◽  
Resting Cells ◽  
Resting Cell ◽  
Transport Chain ◽  
Oxidation Of Glucose ◽  
Phosphate Incorporation ◽  
Stimulation Of

Resting cell suspensions of Pseudomonas aeruginosa exhibited substrate-dependent phosphorylation and most of the phosphate appeared in the nucleic acid fraction. The amount of P32 incorporated was a function of substrate concentration. When equivalent amounts of glucose, gluconate, or 2-ketogluconate were used as substrate, it was found that the more oxidized substrates supported appreciably less P32 incorporation, thus indicating that phosphorylation is coincident with the passage of electrons to oxygen by way of the electron transport chain. These data serve to illustrate that the practice of determining the amount of energy available from the dissimilation of a substrate by measuring growth yield can be in error since equivalent quantities of glucose, gluconate, and 2-ketogluconate supported equal amounts of growth. The P:O ratios obtained with glucose as substrate were of the order of 0.01. Phosphorylation was not sensitive to dinitrophenol or sodium fluoride but was completely inhibited by cyanide. Chloramphenicol, at a concentration which inhibited protein synthesis, caused a twofold stimulation of phosphate incorporation. Pyocyanine, which stops the oxidation of glucose at the 2-ketogluconate stage, completely inhibited phosphate uptake. The action of pyocyanine on both oxidation and phosphorylation could be reversed by magnesium. When extracts of this organism were studied, it was found that under all conditions the addition of oxidizable substrates decreased P32 incorporation.

Interaction of PGF2α with prolactin on the release of cyclic AMP and progesterone from the isolated perfused ovary of the pregnant mare serum gonadotropin-treated rat

1986 ◽  
Vol 113 (3) ◽  
pp. 410-417 ◽  
Author(s):  
Jan Sogn ◽  
Gun Abrahamsson ◽  
Per O. Janson
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Pregnant Mare Serum Gonadotropin ◽  
Progesterone Secretion ◽  
Site Of Action ◽  
Serum Gonadotropin ◽  
Rat Ovary ◽  
Camp Formation ◽  
Isolated Rat ◽  
Stimulation Of

Abstract. A newly developed model for perfusion of the isolated rat ovary was employed to study the interactions of Prl with PGF2α in respect to the effects of LH on cAMP formation and progesterone production in the 5 day old corpus luteum of the PMSG-treated rat. An inhibitory effect of PGF2α on both basal and LH stimulated progesterone secretion was found. This block also involved inhibition of the ovarian cAMP release which was not associated with a reduction of the flow of the medium to the ovary. When Prl was present in the medium the PGF2α block of LH-induced cAMP release was reversed. However, Prl failed to restore block of LH stimulation of progesterone secretion in 4 out of 9 experiments, indicating an additional site of action of PGF2α distal to the cAMP in these experiments.

Evidence for differential effects of noradrenaline and somatostatin on intracellular messenger systems in rat islets of Langerhans

1990 ◽  
Vol 4 (3) ◽  
pp. 231-237 ◽  
Author(s):  
R. D. Hurst ◽  
N. G. Morgan
Keyword(s):  
Insulin Secretion ◽  
Cyclic Amp ◽  
Islet Cell ◽  
Inhibitory Effect ◽  
Minor Influence ◽  
Rat Islets Of Langerhans ◽  
A Minor ◽  
Intracellular Messenger ◽  
Inhibit Insulin Secretion ◽  
Stimulation Of

ABSTRACT The mechanisms involved in inhibition of insulin secretion by somatostatin and noradrenaline were compared in order to establish whether the receptors for these agents are coupled to similar effector systems in the pancreatic B cell. Both agents significantly reduced forskolin-induced adenylate cyclase activity in islet homogenates, although noradrenaline was more effective than somatostatin. The capacity of noradrenaline to inhibit insulin secretion was largely unaffected by agents that increase intracellular cyclic AMP, whereas the effect of somatostatin as an inhibitor was markedly reduced under these conditions. Both noradrenaline and somatostatin inhibited the stimulation of insulin secretion induced by K+ depolarization, but different mechanism were involved. Somatostatin significantly inhibited K+-stimulated 45Ca2+ efflux and influx in islets, while noradrenaline exerted only a minor influence on these processes. The data indicate that noradrenaline controls insulin secretion by a mechanism which operates beyond the level of intracellular messenger generation. In contrast, somatostatin exerts at least part of its inhibitory effect on insulin secretion by directly controlling islet cell Ca2+ influx in a manner which may be regulated by cyclic AMP.

scholarly journals Mechanism of 3-phenylpyruvate-induced insulin release. Secretory, ionic and oxidative aspects

1983 ◽  
Vol 210 (3) ◽  
pp. 913-919 ◽  
Author(s):  
A Sener ◽  
M Welsh ◽  
P Lebrun ◽  
P Garcia-Morales ◽  
M Saceda ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Inhibitory Effect ◽  
Secretory Response ◽  
Acid Transport ◽  
O2 Uptake ◽  
Net Uptake ◽  
High Concentrations ◽  
Stimulation Of

1. 3-Phenylpyruvate caused a dose-related stimulation of insulin release from rat pancreatic islets deprived of exogenous nutrient or incubated in the presence of 5.6 or 8.3 mM-D-glucose. 2. 3-Phenylpyruvate inhibited insulin release evoked by high concentrations of D-glucose (16.7 or 27.8 mM) or 4-methyl-2-oxopentanoate (10.0 mM). This inhibitory effect appeared to be attributable to impairment of 2-oxo-acid transport into the mitochondria, with resulting inhibition of D-glucose, pyruvate or 4-methyl-2-oxopentanoate oxidation. 3. 3-Phenylpyruvate failed to affect the oxidation of, and secretory response to, L-leucine, and did not augment insulin release evoked by a non-metabolized analogue of the latter amino acid. 4. L-Glutamine augmented 3-phenylpyruvate-induced insulin release. The release of insulin evoked by the combination of 3-phenylpyruvate and L-glutamine represented a sustained phenomenon, abolished in the absence of extracellular Ca2+ or the presence of menadione and potentiated by theophylline. 5. Whether in the presence or in the absence of L-glutamine, the secretory response to 3-phenylpyruvate coincided with an increase in O2 uptake, a decrease in K+ conductance, a stimulation of both Ca2+ inflow and 45Ca2+ net uptake and an increase in cyclic AMP content. 6. It is concluded that the release of insulin induced by 3-phenylpyruvate displays features classically encountered when the B-cell is stimulated by nutrient secretagogues, and is indeed attributable to an increase in nutrient catabolism.

Antiplatelet Effects of Ticlopidine Are Reduced in Experimental Hypercholesterolemia

1994 ◽  
Vol 71 (01) ◽  
pp. 112-118 ◽  
Author(s):  
Thomas Hohlfeld ◽  
Frank Scharnowski ◽  
Marina Braun ◽  
Karsten Schrör
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Minor Role ◽  
Standard Diet ◽  
Cyclic Amp Accumulation ◽  
Experimental Hypercholesterolemia ◽  
A Minor ◽  
Induced Aggregation ◽  
Stimulation Of

SummaryThis study determines the antiplatelet effects of oral ticlopidine (100 mg/kg × day) in experimental hypercholesterolemia. Rabbits were fed either a standard diet or a cholesterol-enriched diet (0.5% for 3 months, 1% for 1 month). In normocholesterolemic controls ADP-, but not collagen-induced platelet aggregation was inhibited by ticlopidine treatment. This was accompanied by a significantly enhanced inhibition of ADP-induced platelet aggregation and stimulation of cyclic AMP accumulation by iloprost. Hypercholesterolemia considerably attenuated the inhibition of ADP-induced aggregation by ticlopidine but did not change its effect on the iloprost-induced inhibition of platelet function and cyclic AMP formation. ADP-induced platelet-derived Llnumbuxane formation was considerably greater in hypercholesterolemic rabbits and not reduced by ticlopidine. Ticlopidine did also not significantly influence the extent and severity of atherosclerotic plaque formation although a tendency for improvement was observed in a subgroup of animals. The data suggest that hypercholesterolemia attenuates the inhibitory effect of ticlopidine on A DP-induced platelet aggregation. This might be related to the stimulation of thromboxane formation by ADP in hypercholesterolemia. The maintained protection from ADP-induced inhibition of cAMP accumulation suggests a minor role of this mechanism in the progression of hypercholesterolemia-induced vessel disease in this model.

scholarly journals High concentrations of exogenous arachidonate inhibit calcium mobilization in platelets by stimulation of adenylate cyclase

1988 ◽  
Vol 253 (1) ◽  
pp. 255-262 ◽  
Author(s):  
M A Kowalska ◽  
A K Rao ◽  
J Disa
Keyword(s):  
Arachidonic Acid ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Inhibitory Effect ◽  
Irreversible Damage ◽  
Fura 2 ◽  
Messenger Molecules ◽  
Thromboxane Production ◽  
High Concentrations ◽  
Stimulation Of

1. Exposure of platelets to exogenous arachidonic acid results in aggregation and secretion, which are inhibited at high arachidonate concentrations. The mechanisms for this have not been elucidated fully. In our studies in platelet suspensions, peak aggregation and secretion occurred at 2-5 microM-sodium arachidonate, with complete inhibition around 25 microM. 2. In platelets loaded with quin2 or fura-2, the cytoplasmic Ca2+ concentration, [Ca2+]i, rose in the presence of 1 mM-CaCl2 from 60-80 nM to 300-500 nM at 2-5 microM-arachidonate, followed by inhibition to basal values at 25-50 microM. Thromboxane production was not inhibited at 25 microM-arachidonate. Cyclic AMP increased in the presence of theophylline, from 3.5 pmol/10(8) platelets in unexposed platelets to 8 pmol/10(8) platelets at 50 microM-arachidonate; all platelet responses were inhibited with doubling of cyclic AMP contents. 3. The adenylate cyclase inhibitor 2′,5′-dideoxyadenosine attenuated the inhibitory effect of arachidonate, suggesting that it is mediated by increased platelet cyclic AMP and that it is unlikely to be due to irreversible damage to platelets. 4. Aspirin or the combined lipoxygenase/cyclo-oxygenase inhibitor BW 755C did not prevent the inhibition by arachidonate of either [Ca2+]i signals or aggregation induced by U46619. 5. Thus high arachidonate concentrations inhibit Ca2+ mobilization in platelets, and this is mediated by stimulation of adenylate cyclase. High arachidonate concentrations influence platelet responses by modulating intracellular concentrations of two key messenger molecules, cyclic AMP and Ca2+.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

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