Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of cyclic AMP in cell proliferation and division has been the subject of study by a number of investigators in the past 30 years, but the argument of whether cyclic AMP is a negative or a positive regulator has not been settled. We studied the effect of cyclic AMP on proliferation of normal and postpneumonectomized lung tissues in young adult rats by measuring the incorporation of tritiated thymidine into lung DNA in organ culture. In normal lung tissues the incorporation of [3H]thymidine was increased by exogenous dibutyryl cyclic AMP, or by isoproterenol or forskolin to stimulate adenylate cyclase, or by caffeine, which inhibits cAMP phosphodiesterase. The effect of isoproterenol, but not forskolin, was abolished by the beta-adrenergic blocking agent propranolol. The effect of caffeine on [3H]thymidine incorporation was further enhanced in normal lung tissues in the presence of dibutyryl cyclic AMP and in postpneumonectomized lung tissues. Imidazole, a cAMP phosphodiesterase stimulator, also increased [3H]thymidine incorporation in culture, but the effect was not magnified in the presence of exogenous dibutyryl cyclic AMP, nor in postpneumonectomized lung tissues. The data suggest that cyclic AMP acts as a positive regulator in proliferation of lung tissues.
...
PMID:Role of cyclic AMP in proliferation of lung tissue in organ culture. 254 31

We have been using sporogenous mutants of Dictyostelium discoideum strain V12M2 to study regulation of cell fate during terminal differentiation of spores and stalk cells. Analyses of intracellular cAMP accumulation, cAMP secretion, cAMP binding to cell surface receptors, and chemotactic sensitivity to exogenous cAMP during aggregation showed that all of these functions were identical in V12M2 and HB200, a sporogenous mutant. We used several methods of altering intracellular cAMP levels in HB200 cells to test the hypothesis that intracellular cAMP levels affect cell fate. First, HB200 amoebae were treated with 5 mM caffeine for 4 h during growth, washed, and allowed to develop in the absence of caffeine. Treated cells had normal levels of intracellular cAMP and adenylate cyclase activities at the beginning of differentiation; by 6 h development, they contained two to three times more intracellular cAMP and two times more GTP-dependent adenylate cyclase activity than untreated cells. However, their level of basal Mn++-dependent adenylate cyclase activity was the same as untreated controls. Thus, treatment of growing HB200 amoebae with caffeine for only 4 h leads to hyperinduction of a GTP-dependent regulator (or inhibition of a negative regulator) of adenylate cyclase during subsequent differentiation, without induction of basal activity. The fraction of amoebae forming spores increased twofold when HB200 amoebae were treated with caffeine during growth. Spore (but not stalk cell) differentiation by such treated cells was blocked by inhibitors of cAMP accumulation. Second, cells grown on nutrient agar accumulated higher levels of intracellular cAMP and formed more spores in vitro than cells grown in shaken suspension.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Conditions that elevate intracellular cyclic AMP levels promote spore formation in Dictyostelium. 255 18

1. Cyclic AMP metabolism was studied in intact and intracellularly perfused axons. 2. Cyclic AMP content of intact axons lay within the range 10-100 nmol kg-1 axoplasm. This was increased by exposure to caffeine (2-fold) and to 5-HT (15-fold). The caffeine-sensitive cyclic AMP increase was 30-fold larger in the presence of 5-HT. 3. A reduction in sodium concentration from the sea water bathing intact axons attenuated the 5-HT-evoked increase in cyclic AMP content, but had little effect on resting cyclic AMP. This effect was partially reversed by exclusion of external calcium, and suggests that free calcium plays a role in cyclic AMP homeostasis. 4. Prolonged exposure of intact axons to 5-HT (up to 3 h) led to apparent desensitization of the cyclic AMP response. 5. Intracellular perfusion can be used as a method to study adenylate cyclase in a single axon, simply by measuring the cyclic AMP content of the emerging perfusate. 6. Intracellular perfusion revealed micromolar requirements for internal GTP (K0.5 approximately 1-10 microM) and external 5-HT (K0.5 approximately 1-10 microM); a detailed investigation of this observation was limited due to the progressive loss of 5-HT-evoked adenylate cyclase activity with time. This slow loss was not seen during Gpp(NH)p (guanylylimidodiphosphate), NaF or forskolin activation of cyclase activity. 7. In perfused axons, an increase in intracellular calcium stimulated cyclase activated by 100 microM-forskolin but inhibited cyclase activated by 500 microM-Gpp(NH)p or 10 mM-NaF. A reduction in intracellular magnesium from 10 to 4-5 mM attenuated the effects of 5-HT-evoked cyclase activity. 8. Study of the perfused axon allows characterization of the intracellular requirements of a plasmalemmal transduction system which activates adenylate cyclase, whilst maintaining ionic asymmetry across the cell membrane.
...
PMID:Characteristics of a 5-hydroxytryptamine-sensitive adenylate cyclase in intact and intracellularly perfused squid axons. 256 84

Purine nucleotides and their metabolites are important mediators of vascular tone. Adenosine promotes relaxation of vascular smooth muscle, acting on the A2 subclass of purinoceptors. There is some evidence that these receptors are also present on vascular endothelial cells. We have therefore examined cultured aortic endothelial cells for adenosine (A2) sensitivity. Bovine aortic endothelial cells (AG4762) were obtained from the Institute of Aging cell repository (USA), and cultured in monolayer flasks. Adenylate cyclase activity in homogenates of AG4762 cells was increased by 5'-(N-ethylcarboxamido)-adenosine (NECA) greater than 2-chloroadenosine greater than adenosine. NECA dependent activation of adenylate cyclase was inhibited by 3-isobutyl-l-methylxanthine greater than theophylline greater than caffeine. The rank order of potency of these compounds identified the responses as mediated by A2 purinoceptors. Prolonged exposure of AG4762 cells to NECA in culture resulted in loss of A2 purinoceptor responsiveness, and purinoceptor activity could be restored to non-dividing densensitized cells by further culture in the absence of the desensitising agent. The cyclic AMP dependent phosphorylation of specific sites in endothelial cells may trigger a number of important biological events which are yet to be determined.
...
PMID:Expression and desensitisation of A2 purinoceptors on cultured bovine aortic endothelial cells. 259 Sep 13

In homogenates of NG108-15 cells, adenosine analogues activate adenylate cyclase with the following order of potency: N-ethylcarboxamidoadenosine (NECA) greater than 2-chloroadenosine greater than N6-(L-phenylisopropyl)-adenosine (PIA) = cyclohexyladenosine = 2-phenylaminoadenosine. Adenosine receptor antagonists inhibit NECA-stimulated adenylate cyclase activity with the order of potency 3-isobutyl-1-methyl-xanthine (IBMX) greater than theophylline greater than caffeine. These data suggest that these ligands act at an adenosine A2 receptor. There is an apparently homogenous population of saturable 3H-NECA binding sites in homogenates of NG108-15 cells. These sites have an affinity for 3H-NECA of approximately 1 microM, and are present at a density of approximately 10 pmol/mg protein. Unlabelled NECA, 2-chloroadenosine, IBMX and theophylline displace 3H-NECA binding, with an order of potency that suggests that the 3H-NECA binding site may represent an adenosine A2 receptor. However, PIA, cyclohexyladenosine and 2-phenylaminoadenosine produce no detectable displacement of 3H-NECA binding at concentrations that produce a maximal stimulation of adenylate cyclase activity. Pretreatment of NG108-15 cells with either NECA or PIA produces a homologous desensitization of subsequent responses to all the adenosine analogues, with no effect on subsequent responses to a prostacyclin receptor agonist or NaF. This suggests that all the adenosine analogues examined activate an adenosine A2 receptor. Therefore, the 3H-NECA site at which PIA is inactive cannot represent this receptor.
...
PMID:A selective binding site for 3H-NECA that is not an adenosine A2 receptor. 259 74

The maturation of brittle-star (Amphipholis kochii) oocytes, i.e., the reinitiation of meiosis accompanied by germinal vesicle breakdown (GVBD) and the acquisition of fertilizability, was induced by acid (pH 3.0) seawater containing 10 mM cAMP. Oocyte maturation was also induced by seawater of normal pH (pH 8.0) that contained either an inhibitor of cyclic nucleotide phosphodiesterase (25 mM theophylline, 25 mM caffeine) or an activator of adenylate cyclase (100 microM forskolin, 0.6 microM cholera toxin). Experiments in which the oocytes were treated with forskolin or theophylline for various periods of time demonstrated that there was a positive correlation between the oocyte cAMP level measured by radioimmunoassay and the extent of GVBD induced in each treatment: both increased as the treatment period became longer and about a threefold increase in cAMP level induced 50% GVBD. These results indicate that an increase in cAMP level initiates maturation of the brittle-star oocytes.
...
PMID:Involvement of cAMP in initiating maturation of the brittle-star Amphipholis kochii oocytes: induction of oocyte maturation by inhibitors of cyclic nucleotide phosphodiesterase and activators of adenylate cyclase. 282 56

We have examined the regulation of three early developmentally regulated genes in Dictyostelium. Two of these genes (D2 and M3) are induced by pulses of cAMP and the other (K5) is repressed. Expression of these genes has been examined in a number of developmental mutants that are specifically blocked in various aspects of the signal transduction/cAMP relay system involved in aggregation and control of early development. The mutant strains include Synag mutants, which are blocked in receptor-mediated activation of adenylate cyclase and do not relay cAMP pulses; FrigidA mutants, which are blocked in receptor-mediated activation of both adenylate cyclase and the putative phosphoinositol bisphosphate (PIP2) turnover pathway and appear to be mutations in the gene encoding one of the G alpha protein subunits; and a StreamerF allele, which lacks cGMP-specific cGMP phosphodiesterase. From the analysis of the developmental expression of these genes under a variety of conditions in these mutant strains, we have drawn a number of conclusions concerning the modes of regulation of these genes. Full induction of D2 and M3 genes requires cAMP interaction with the cell surface receptor and an "oscillation" of the receptor between active and adapted forms. Induction of these genes does not require activation of the signal transduction pathway that leads to adenylate cyclase activation and cAMP relay, but does require activation of other receptor-mediated intracellular signal transduction pathways, possibly that involving PIP2 turnover. Likewise, repression of the K5 gene requires pulses of cAMP. Expression of this gene is insensitive to cAMP pulses in FrigidA mutants, suggesting that a signal transduction pathway is necessary for its repression. Results using the StreamerF mutant suggest that the rise in cGMP in response to cAMP/receptor interactions may not be directly related to control of the pulse-induced genes. In addition, we have examined the effect of caffeine, which M. Brenner and S.D. Thomas (1984, Dev. Biol., 101, 136-146) showed preferentially blocks the cAMP relay system by blocking receptor-mediated activation of adenylate cyclase. We show that in many of the mutants and in an axenic wild-type strain, caffeine causes the induction of pulse-induced gene expression to almost wild-type levels or in some cases to higher than wild-type levels. Our data suggest that caffeine works by activating some step in the signal transduction pathway that must lie downstream from both the receptor and at least one of the G proteins and thus has effects other than simply blocking the receptor-mediated cAMP relay system.
...
PMID:cAMP regulation of early gene expression in signal transduction mutants of Dictyostelium. 284 88

The effects of feeding a diet enriched in caffeine or carbamazepine (CBZ) were investigated in rats in a quantitative autoradiographic study of adenosine A1 receptors (labeled by [3H]cyclohexyladenosine, [3H]CHA) and adenylate cyclase (labeled by [3H]forskolin). Although regional distribution of [3H]CHA and [3H]forskolin binding sites differed in some areas, chronic CBZ as well as chronic caffeine upregulated both of them. The changes in receptor densities occurred in the same brain microregions, suggesting that caffeine and CBZ act as antagonists at similar subpopulations of adenosine A1 receptors and [3H]forskolin binding sites. Therefore, a selective interaction of these two drugs with distinct adenosine A1 receptors (and adenylate cyclase) probably does not explain the differential effects of caffeine and CBZ on neuronal activity.
...
PMID:Upregulation of adenosine A1 receptors and forskolin binding sites following chronic treatment with caffeine or carbamazepine: a quantitative autoradiographic study. 291 15

The phosphodiesterase inhibitors caffeine, theophylline, aminophylline and isobutyl-methylxanthine (IBMX) were found to inhibit induction of morphologically transformed hamster embryo cell colonies by sequential exposure to benzo[a]pyrene (BaP) and the tumor promoter TPA. Almost complete inhibition of cell transformation was observed when 50 micrograms/ml theophylline, aminophylline, IBMX, or 200 micrograms/ml caffeine was present together with the tumor promoter. The compounds had no effect on the transformation frequency when present together with the initiator, BaP, in the first exposure period. Substances that stimulate the adenylate cyclase and the addition of exogenous dibutyryl-cAMP had similar inhibitory effects.
...
PMID:Caffeine and other phosphodiesterase inhibitors are potent inhibitors of the promotional effect of TPA on morphological transformation of hamster embryo cells. 299 64

Cyclic AMP stimulation of chemotactically competent Dictyostelium amebas labeled with [32P]orthophosphate transiently increases phosphorylation in the heavy chain and the 18,000 dalton light chain of myosin. Immediately before the increase, heavy chain phosphorylation transiently decreases. These phosphorylation changes also occur when cAMP-induced activation of adenylate cyclase is blocked by pretreatment of amebas with caffeine. The time course of these phosphorylation responses correlates with the shape changes induced in amebas exposed to a temporal increase in cAMP concentration. The dose dependence of the phosphorylation responses is the same as that previously determined for chemotaxis. The phosphorylation responses exhibit adaptation properties in common with those of the shape change response and chemotaxis. Increases in the rate of myosin heavy chain and light chain phosphorylation can be observed in vitro by stimulating unlabeled amebas with cAMP and then lysing the cells into a gamma-[32P]ATP-containing reaction mixture.
...
PMID:Chemoattractant-elicited increases in myosin phosphorylation in Dictyostelium. 300 Jun 4


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

---