SEARCH · Search PubMed

Results for “AMPs”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources

PubMed1988

Effects of suboptimal levels of extracellular calcium on the regulation of the cyclic AMP phosphodiesterase-inhibitor system and membrane differentiation in Dictyostelium discoideum.

When starved wild-type amoebae of Dictyostelium discoideum were washed and incubated in 1 mM-EGTA, their ability to induce soluble cyclic AMP phosphodiesterase (PD) activity in response to either millimolar cyclic AMP or a series of nanomolar cyclic AMP pulses was reduced by 55-75%. Supplementation of EGTA-treated cells with exogenous Ca2+ stimulated PD induction in a dose-dependent fashion (EC50 = 100-200 nM free extracellular Ca2+), and enzyme production was maximal at about 1 microM free Ca2+. Ca2+ depletion also strongly impaired production of the phosphodiesterase inhibitor (PDI). In contrast, other than delaying their appearance by about 1 h, EGTA had little effect on the induction by cyclic AMP pulses of cell surface markers such as contact sites A and membrane-bound PD activity. Similar changes in both the soluble and membrane activities were observed with strain NP368, a mutant that overproduces cyclic GMP when stimulated by cyclic AMP. Thus, Ca2+ depletion does not appear to inhibit PD and PDI production by reducing intracellular cyclic GMP. To determine whether Ca2+ depletion alters signal transduction, two mutants that produce the soluble PD activities constitutively were examined. Suboptimal concentrations of free extracellular Ca2+ were found to inhibit PD production in these cells to the same degree and with the same concentration dependence as low Ca2+ inhibited PD induction by cyclic AMP in wild-type cells. These results suggest that Ca2+ depletion by EGTA probably inhibits PD and PDI production indirectly by perturbing an intracellular Ca2+ pool(s) rather than by altering a surface cyclic AMP-receptor-mediated process.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1990

Changes in cyclic AMP receptor properties during adaptation in Dictyostelium discoideum.

In developing Dictyostelium discoideum cells, binding of cyclic AMP to the chemotactic receptor has been shown to oscillate. These oscillations represent cycles of activation, adaptation and deadaptation of the cyclic AMP receptor system. We studied the molecular basis of these oscillatory changes in cyclic AMP receptor binding. We developed a rapid method of lysing cells during the course of the oscillations. This method guaranteed good preservation of ligand binding properties of the cyclic AMP receptor. We found that oscillations in cyclic AMP binding resulted from changes in receptor affinity. The total number of receptors did not significantly change during oscillations. Our experiments also showed that both GTP and GDP abolished oscillations in receptor binding completely, presumably by acting via a G protein. The guanine nucleotides reduced the affinity of the receptor at all time-points of the oscillation cycle to the minimal, i.e. adapted, level. We conclude that the cyclic process of activation, adaptation and de-adaptation in D. discoideum, at cyclic AMP receptor level, involves changes in receptor-G protein interaction. During adaptation, the affinity of the cyclic AMP receptor decreases and the receptor becomes insensitive to guanine nucleotides.

Adaptation, Physiological↗

PubMed1978

Cyclic AMP metabolism in adipose tissue of exercise-trained rats.

Cyclic AMP metabolism in epididymal adipose tissue of exercise-trained rats was examined to determine if training induced changes in cyclic AMP production or inactivation. Beginning at 7 weeks of age, male rats were physically trained by 12 weeks of treadmill running. Pair-fed control rats remained sedentary in their cages for the duration of the experiment. Tissue levels of cyclic AMP were measured in epididymal adipose tissue slices incubated with norepinephrine. Adenyl cyclase was assayed in adipocyte ghost cell prepartions and low-Km phosphodiesterase was assayed in homogenates of adipose tissue. In response to norepinephrine stimulation, tissue cyclic AMP levels were reduced in trained compared to untrained rats. Training increased the ratio of activity of phosphodiesterase relative to adenyl cyclase. The results of this study indicate that cyclic AMP production in response to norepinephrine stimulation is not increased by training and may even be reduced, implying that adipose tissue cyclic AMP levels may be under a greater degree of control in trained rats. Modulation of adipose tissue cyclic AMP levels may function to regulate more closely the duration of lipolysis in exercise-trained rats.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1989

Model of prostaglandin-regulated cyclic AMP metabolism in intact platelets: examination of time-dependent effects on adenylate cyclase and phosphodiesterase activities.

The kinetics of prostaglandin-regulated cyclic AMP formation by intact human platelets were studied in the presence and absence of phosphodiesterase inhibitors. In the case of iloprost, a chemically stable analogue of prostaglandin I2, the shape of the time course varied with prostaglandin concentration. In the presence of phosphodiesterase inhibitors, low concentrations of iloprost gave a linear rate of cyclic AMP formation. At higher concentrations of iloprost, the initial rate increased as a saturable function of prostaglandin concentration but the curves decayed with time to give new linear rates of cyclic AMP formation with a different prostaglandin concentration dependence from the initial rates. Time courses were simulated using KINSIM [Anal. Biochem. 130: 134-145 (1983)], a kinetic simulation program that employs numerical integration, over a wide range of iloprost concentration (3 nM to 30 microM) by use of a simple model involving rapid activation of adenylate cyclase, followed by slow reversible transition of adenylate cyclase to an inactive form (desensitization) through a distinct inhibitory receptor. The model requires that the affinity for prostaglandins of both the stimulatory and inhibitory receptors declines with prostaglandin concentration, which may be related to the existence of high and low affinity receptor forms depending on the activation state of the appropriate GTP-binding protein. The same two-receptor model can be used to describe cyclic AMP metabolism in the absence of phosphodiesterase inhibitors, giving rise to characteristic peak and plateau effects in the time courses. The putative inhibitory receptor has an apparent affinity for prostaglandin lower than the stimulatory receptor in the case of iloprost and a higher affinity than the stimulatory receptor in the case of prostaglandin E1. The contribution of phosphodiesterase activation to the time course of cyclic AMP formation through phosphorylation by cyclic AMP-dependent protein kinase was assessed. It was shown that phosphodiesterase activation must be rapid. A plausible and perhaps complete description of prostaglandin-regulated cyclic AMP metabolism in platelets is presented.

1-Methyl-3-isobutylxanthine↗

PubMed1980

Hypothesis. Cyclic AMP and its receptor protein in tumor growth regulation in vivo.

A working hypothesis is presented to elucidate the action of cyclic AMP in the regulation of tumor growth in vivo. The formation and nuclear translocation of a complex consisting of cyclic AMP, its receptor binding protein, and the catalytic unit of protein kinase are the indispensable events necessary to trigger the regression of hormone-dependent mammary tumors. If the integrity of the cyclic AMP receptor molecule is not preserved and the cyclic AMP concentration is not physiological, the above processes do not occur and tumors remain hormone-unresponsive. It is therefore postulated that arrest of tumor growth in vivo depends upon the structural integrity of the cyclic AMP receptor protein and the optimum cellular concentration of cyclic AMP, which make possible the formation and nuclear translocation of the cyclic AMP receptor complex.

Animals↗

PubMed1984

Purification of intact and nicked forms of a zinc-containing, Mg2+-dependent, low Km cyclic AMP phosphodiesterase from bakers' yeast.

A low Km cyclic AMP phosphodiesterase was purified to homogeneity from microsomes of bakers' yeast. "Intact" enzyme, purified from microsomes prepared in the presence of the protease inhibitor phenylmethylsulfonyl fluoride, had a specific activity of 0.6 mumol/min/mg of protein (30 degrees C, pH 8.0, 1 microM cyclic AMP), a pI of 6.65 +/- 0.15, and a molecular weight of 61,000 determined by gel electrophoresis in the presence of sodium dodecyl sulfate. Gel filtration of native enzyme suggested it is a monomer. When phenylmethylsulfonyl fluoride was omitted, a product ("nicked" enzyme) was obtained with a specific activity of 1.2 mumol/min/mg of protein, the same pI, and a similar amino acid composition; but gel electrophoresis now showed two bands, with molecular weights of 45,000 and about 17,000, together with a small amount of the 61,000 band. Apart from the higher specific activity of the nicked enzyme, no difference was found between the catalytic properties of the two enzyme forms. Between 40 nM and 1 microM cyclic AMP, an apparent Km of 170 nM was observed at pH 8.0, but at higher cyclic AMP concentrations (2-30 microM), Hofstee plots curved upwards. Cyclic deoxy-AMP was a substrate, but cyclic GMP was not and did not affect the activity towards cyclic AMP. Both enzyme forms contained tightly bound zinc. The metal chelators, 8-hydroxyquinoline and orthophenanthroline , caused progressive partial inactivation of the enzyme and a decrease in its affinity for cyclic AMP. Dialysis against Zn2+, Cu2+, Co2+, or Mn2+ (but not Mg2+ or Ni2+) reversed these changes.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1975

Cyclic AMP response to epinephrine and shock.

Hormonal regulation is fundamental to homeostasis, and the response in tissues is mediated by adenosine 3':5' equals cyclic phosphate (cyclic AMP). Since circulating levels of catecholamines are elevated during hemorrhagic shock, experiments were carried out to study the effects of epinephrine and of shock on cyclic AMP levels of plasma and of the intestine, a particularly vulnerable organ in canine hemorrhagic shock. Epinephrine was given to normotensive dogs as a constant infusion (group 1) or as a single pulse (group 2). Sequential blood samples showed a marked increase in circulating cyclic AMP, especially in portal and hepatic venous blood. Little change was noted in the tissues. Hemorrhagic shock (group 3) induced a marked increase in plasma cyclic AMP, with a depletion of mucosal cyclic AMP and adenosine triphosphate (ATP). Pretreatment before shock with alpha-blockade (group 4) abolished the decrease in mucosal cyclic AMP and ATP, and reduced the increase in plasma cyclic AMP.

Acepromazine↗

PubMed1996

Control of retinoic acid receptor expression in mouse melanoma cells by cyclic AMP.

Retinoic acid receptor (RAR) alpha and gamma mRNAs were constitutively expressed in B16 melanoma cells with or without retinoic acid (RA) treatment. RAR beta mRNA, however, was significantly expressed only after exposure to RA. Induction of RAR beta by RA occurred within 1 h and was not inhibited by cycloheximide (i.e., did not require new protein synthesis). All three RAR mRNA levels were dramatically decreased with 8-bromo-cyclic AMP treatment and could not be rescued by addition of RA. Analysis of RAR gamma revealed that this decrease occurred within 1 h of exposure to 8-bromo-cyclic AMP and was not blocked by simultaneous treatment with cycloheximide. The stability of RAR gamma mRNA was not altered by cyclic AMP treatment. Nuclear extracts from 8-bromo-cyclic AMP-treated cells showed a large decrease in protein binding to a retinoic acid response element (RARE) oligonucleotide compared to control cells. This correlated with a marked reduction of RA-stimulated RARE-reporter gene activity in transfected cells which were treated with cyclic AMP. Pretreatment of B16 cells with cyclic AMP prior to RA addition dramatically reduced induction of PKC alpha, an early marker of RA-induced cell differentiation. Thus, cyclic AMP can antagonize the action of RA most likely via its ability to inhibit RAR expression.

1-Methyl-3-isobutylxanthine↗

PubMed1985

Oscillations and cyclic AMP-induced changes of the K+ concentration in Dictyostelium discoideum.

By means of a K+-sensitive electrode, the extracellular K+ concentration was monitored in cell suspensions of Dictyostelium discoideum. In aggregative cells the attractant cyclic AMP induced a transient release of K+. The response was detectable within 6-12 s and peaked at 30-40 s. The apparent rate of release amounted to 7 X 10(8)K+ ions per cell per min. Adenosine and 5' AMP, which are chemotactically inactive, did not elicit measurable K+ responses. The cyclic AMP-induced release of K+ depended on the state of differentiation of the cells. In undifferentiated cells cyclic AMP did not cause a measurable K+ release, whereas folic acid, a potent attractant at this cell stage, induced a weak but significant K+ response. The cyclic AMP-induced K+ release in aggregative cells was inhibited by K+-channel blockers such as quinine and tetraethylammonium. In suspensions of differentiated cells free running oscillations of the extracellular K+ concentration were observed. K+ oscillations were related to cyclic AMP oscillations and oscillations of the light-scattering properties of cells. Cells continuously released NH4+; however, cyclic AMP did not induce a measurable change of NH4+ release.

Ammonia↗

PubMed1986

Actions of calcitonin, parathyroid hormone, and prostaglandin E2 on cyclic AMP formation in chicken and rat osteoclasts.

The effects of calcitonin, parathyroid hormone, and prostaglandin E2 on cyclic AMP production were studied in osteoclast-rich cultures derived from medullary bone of laying hens and from the long bones of newborn rats. Cyclic AMP was assayed biochemically in replicate cultures, and furthermore, changes in cytoplasmic fluorescence were sought by indirect immunofluorescence with rabbit anti-cyclic AMP and FITC-labelled goat anti-rabbit IgG. Treatment of rat osteoclasts with calcitonin increased cyclic AMP formation as measured biochemically, and this was confirmed by the immunofluorescence method. No such increase took place in chick osteoclasts. Prostaglandin E2 increased cyclic AMP production in both rat and chick osteoclasts as determined by both methods. Since the immunofluorescence method failed to detect a response to parathyroid hormone either in chick or rat osteoclasts, its variable biochemical effects were concluded to be due to actions on contaminating osteoblasts in the cultures. Thus it has been possible with a combined biochemical and immunocytochemical approach to define the cyclic AMP responses to the calcium-regulating hormones in rat and chick osteoclasts. The failure of calcitonin to increase cyclic AMP in chick osteoclasts identifies a need to investigate the nature of calcitonin action on avian osteoclasts, which may contribute to understanding of its actions on mammalian cells.

Animals↗

PubMed1978

Effects of cyclic AMP on the growth of differentiating and undifferentiated Friend erythroleukemic cells.

Elevated concentrations of cyclic AMP elicit only minor reductions in growth rate and saturation density in undifferentiated Friend erythroleukemic cells. During the course of dimethylsulfoxide (DMSO)-induced differentiation, Friend cells convert from a cyclic AMP-tolerant state to a phenotype characterized by a high degree of sensitivity to cyclic AMP-mediated growth arrest. Conversion to cyclic AMP sensitivity is detectable after 30 hours growth in medium containing 2% DMSO, and either 0.5 mM 8-Br-cyclic AMP or 5 nM cholera toxin. Cultures of differentiating Friend cells achieved a stationary phase density that was approximately 8-fold higher than the cell density observed in parallel, differentiating cultures treated with 0.5 mM 8-Br-cyclic AMP. Temporally, the appearance of cyclic AMP-sensitivity corresponds to the early expression of in vitro erythroid differentiation (Ross et al., '74), but growth arrest does not alter the subsequent accumulation of hemoglobin in non-dividing DMSO-induced cells. Since growth arrest is preceded by a round of cell division, these observations are consistent with the concept that DMSO must be present during DNA replication for the subsequent expression of hemoglobin synthesis (McClintock and Papaconstantinou, '74; Levy et al., '75; Harrison, '76).

Adenosine Monophosphate↗

PubMed1985

Interactions between cyclic AMP- and phorbol ester-dependent phosphorylation systems in S49 mouse lymphoma cells.

High-resolution two-dimensional gel electrophoresis of proteins labeled with either 32Pi or [35S]methionine was used to study interactions between cyclic AMP and tetradecanoyl phorbol acetate (TPA) at the level of intracellular protein phosphorylation. Cultured S49 mouse lymphoma cells were used as a model system, and mutant sublines lacking either the catalytic subunit of cyclic AMP-dependent protein kinase or the guanyl nucleotide-binding "Ns" factor of adenylate cyclase provided tools to probe mechanisms underlying the interactions observed. Three sets of phosphoproteins responded differently to TPA treatment of wild-type and mutant cells: Phosphorylations shown previously to be responsive to activation of intracellular cyclic AMP-dependent protein kinase were stimulated by TPA in wild-type cells but not in mutant cells, a subset of phosphorylations stimulated strongly by TPA in mutant cells was inhibited in wild-type cells, and two novel phosphoprotein species appeared in response to TPA only in wild-type cells. The latter two classes of TPA-mediated responses specific to wild-type cells could be evoked in adenylate cyclase-deficient cells by treating concomitantly with TPA and either forskolin or an analog of cyclic AMP. Three conclusions are drawn from our results: 1) TPA stimulates adenylate cyclase in wild-type cells causing increased phosphorylation of endogenous substrates by cyclic AMP-dependent protein kinase, 2) activated cyclic AMP-dependent protein kinase inhibits phosphorylation (or enhances dephosphorylation) of a specific subset of TPA-dependent phosphoproteins, and 3) cyclic AMP-dependent events facilitate TPA-dependent phosphorylation of some substrate proteins.

Animals↗

PubMed1980

Studies on AMP deaminase and 5'-nucleotidase in rat brain under different experimental conditions.

Adenosine monophosphate (AMP) deaminase and 5'-nucleotidase, the two enzymes involved in the disposal of AMP, have been detected in different regions of normal rat brain and in animals subjected to heightened neuronal activity (leptazol-induced convulsions) and to depression of the central nervous system (CNS) by the administration of barbiturates. They have also been estimated in the CNS of animals subjected to anoxia or treated with lithium and ammonium salts. The AMP deaminase activity was found to be highest in cerebellum and lowest in cerebral cortex, while the 5'-nucleotidase activity was found to be highest in brain stem and lowest in cerebellum. The AMP deaminase activity was elevated in all the regions of brain during the preconvulsive and convulsive periods. The activity returned to normal during recovery. The activity of 5'-nucleotidase was found to be depressed in the preconvulsive and post-convulsive periods. The enzyme was also found to be depressed in all the three regions after the administration of barbiturates. Administration of lithium or ammonium salts of induction of anoxic states resulted in an increase in the activity of AMP deaminase in all the three regions of brain. These results are discussed in relation to the probable production of cyclic AMP and cyclic guanosine monophosphate (GMP) which may have depressive and excitatory roles, respectively, in brain. It appears that increased AMP deaminase activity is associated with increased neuronal activity while depression of 5'-nucleotidase activity is associated with conditions of decreased CNS excitability.

AMP Deaminase↗

PubMed1988

Activators of protein kinase C enhance cyclic AMP accumulation in cerebral cortical and diencephalic neurons in primary culture.

The effects of the active phorbol ester 12-myristate, 13-acetate (PMA), the inactive ester 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), and the synthetic diacylglycerol 1-oleoyl-2-acetyl-glycerol (OAG) on cyclic AMP production were examined in rat cerebral cortical and diencephalic cells. With the aid of a prelabeling technique for measuring cyclic AMP accumulation in the cells, it was found that neither PMA nor OAG significantly increased cyclic AMP formation in either type of cell. In contrast, PMA enhanced the cyclic AMP response to vasoactive intestinal peptide (VIP) and forskolin in cerebral cortical and diencephalic cells, whereas 4 alpha-PDD was inactive. A 15-min preincubation was used to obtain maximal enhancement. The concentration dependence of PMA on VIP-stimulated cyclic AMP accumulation was determined in cortical cells (EC50 = 6.2 x 10(-8) M). OAG was also able to potentiate VIP-induced cyclic AMP formation in cortical and diencephalic cells. However, its potentiating effect was weaker than that observed with PMA treatment. The data show, at an early stage of development (primary cultures, 8-10 days), a modulation of VIP- or forskolin-cyclic AMP response by the activators of protein kinase C, i.e., PMA and OAG, in two different structures of the central nervous system: the cerebral cortex and the diencephalon. To our knowledge, this is the first demonstration of such a potentiation within the diencephalon.

Animals↗

PubMed1976

The correlation of plasma membrane microvilli and intracellular cyclic AMP content in a rat epitheloid kidney cell line.

Modulation of the intracellular concentration of cyclic AMP has been associated with a regulatory role in cell division, cell morphology, and physical properties of the plasma membrane. Untransformed rat kidney cells in culture exhibit epitheloid morphology, high intracellular cyclic AMP levels, and contact inhibition of growth. Untransformed rat kidney cells transformed with the Kirsten murine sarcoma virus exhibit a low cyclic AMP content, rapid growth rate, and a loss of contact inhibition. Scanning electron microscopy reveals a distinctive difference in the surface structure of the two cell types during Gl of the cell cycle. The surface of the transformed cell is covered with microvilli while its untransformed counterpart is devoid of microvilli. The presence of microvilli can be controlled as a function of temperature by two temperature-sensitive mutants of the Kirsten sarcoma virus (ts6t6 and ts371 cl 5). In the ts6t6 mutant, growth at 32 degrees C results in a low cyclic AMP content and the presence of microville, while growth at 39 degrees C results in a high cyclic AMP content and a decrease in microvilli. The opposite effect is seen with the ts371 cl 5 mutant. Correlation of cyclic AMP content with the presence of microvilli suggests that this surface phenomenon is a function of cyclic AMP concentration.

Cell Division↗

PubMed2000

Differential redistribution of protein kinase C isoforms by cyclic AMP in HL60 cells.

In this study we have analyzed the distribution of protein kinase C isoforms in cytosol, membrane, and nucleus in HL60 cells. Furthermore, we have studied the redistribution of these isoforms after cyclic AMP treatment. Protein kinase C localization and cyclic AMP-induced translocation was demonstrated by Western blot analysis. Cytosol, membrane and nucleus in HL60 cells expressed the abundance of protein kinase C alpha, betaI, betaII, delta, lambda, and zeta isoforms. After cyclic AMP treatment, the amount of protein kinase C betaI and zeta increased only in the nucleus, while protein kinase C delta increased in the three fractions tested. These effects were dependent on the cyclic AMP concentration and duration of action. Our results suggest the existence of cross-talk between the cyclic AMP system and protein kinase C in HL60 cells. Taking into account the processes regulated by protein kinase C, these findings also suggest that cyclic AMP plays a regulatory role in various cellular responses in HL60 cells, such as differentiation and gene expression. The increase observed in PKC delta was due to cyclic AMP-dependent protein kinase C activation, and the synthesis of enzyme was probably activated by the nucleotide.

Biological Transport↗

PubMed1998

Structural-functional relationships in pig heart AMP-deaminase in the presence of ATP, orthophosphate, and phosphatidate bilayers.

The secondary structure of pig heart AMP-deaminase (AMP-d) in the absence and in the presence of orthophosphate or dioleoyl phosphatidic acid (DOPA) or ATP was investigated by FT-IR spectroscopy. While the latter substance activates the enzyme, orthophosphate is a well-known negative allosteric effector and DOPA exerts a noncompetitive inhibition on AMP-deaminase. Small changes in the secondary structure of AMP-d were induced by the above mentioned substances. Only DOPA reduced the thermal stability of AMP-d and avoided protein intermolecular interactions suggesting structural-functional relationships in AMP-d in the presence of the above substances and a possible role of phosphatidic acid in the subtle regulation of AMP-d activity by temporary binding of the enzyme to cellular membranes.

AMP Deaminase↗

PubMed1987

Opposing actions of D-1 and D-2 dopamine receptor-mediated alterations of adenosine-3',5'-cyclic monophosphate (cyclic AMP) formation during the amphetamine-induced release of endogenous dopamine in vitro.

Changes in the formation of cyclic AMP following d-amphetamine (0.1 to 20 mumol/l) were examined in vitro in striatal slices of the rat. d-Amphetamine caused a dose-related increase in cyclic AMP content. This action of d-amphetamine was abolished by tissue pretreatment with reserpine (2.5 mg/kg, i.p.) and 3-iodotyrosine (1 mmol/l). By contrast, both clorgyline (0.1 mumol/l) and nomifensine (30 mumol/l) enhanced the d-amphetamine-induced increase in cyclic AMP formation. In superfusion experiments, a strong correlation between endogenous dopamine and cyclic AMP release was observed before, during and after d-amphetamine exposure. Finally, Sch 23390 (10 mumol/l) abolished while (-)sulpiride (10 mumol/l) enhanced the amphetamine-induced increase in cyclic AMP content. These results suggest that d-amphetamine enhances the formation of cyclic AMP through the release of endogenous dopamine into the synapse where it can interact with both D-1 and D-2 dopamine receptors. These results provide direct evidence that the antagonistic properties of D-1 and D-2 receptors on cyclic AMP formation are apparent at striatal synapses during release of endogenous neuronal dopamine.

Animals↗