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

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

Adenosine rapidly stimulated adenylate cyclase activity but did not modify cyclic AMP degradation when added to a particulate fraction prepared from isolated bone cells. The effect of adenosine was one-half maximal at 5-10 micronM, and was not mimicked by 5' AMP, inosine, guanosine, uridine, adenine, or ribose. Basal and adenosine-stimulated adenylate cyclase activites were directly proportional to the concentration of particulate protein in the assay system. Theophylline decreased the degree to which adenosine stimulated adenylate cyclase activity, whereas another phosphodiesterase inhibitor, RO-20-1724, failed to iiinfluence the effect of adenosine. Adenosine itself, and not a metabolite of adenosine is the stimulator of adenylate cyclase, since it was neither phosphorylated nor deaminated appreciably by the particulate fraction. The particulate fraction did not convert substrate ATP to adenosine in amounts sufficient to enhance adenylate cyclase. The stimulatory effect of adenosine was maximal at 1.2 mM Mg2+, declined with increases in the Mg2+ concentration, and was replaced by inhibition at 20 mM Mg2+. At 2.4 mM Mg2+, basal adenylate cyclase activity peaked at 1.1 mM ATP, and was inhibited by higher ATP concentrations. The magnitude of adenosine stimulation was greater at inhibitory concentrations of ATP than at concentrations which yielded maximum activity. The results suggest that the previously demonstrated ability of adenosine to increase cyclic 3'5' AMP levels in intact bone cells stems from its effect on adenylate cyclase. Adenosine may act by modifying the regulatory nfluence of free Mg2+, uncomplexed ATP, (or both), on adenylate cyclase. Theophylline appears to interfere with the action of adenosine by a mechanism which is distinct from its capacity to inhibit cyclic AMP phosphodiesterase activity. (Endocrinology 99:901,1976)
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PMID:Adenosine-mediated stimulation of bone cell adenylate cyclase activity. 18 72

Adenosine, AMP, ADP and ATP activated adenylate cyclase in pig skin (epidermis) slices resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of the cyclic AMP-phosphodiesterase inhibitor, papaverine. But another inhibitor, theophylline, strongly blocked the activation of adenylate cyclase by adenosine and adenine nucleotides. Theophylline apparently competed with adenosine for the cell surface receptor. Like theophylline, the addition of adenine alone caused no accumulation of cyclic AMP, but it significantly inhibited the stimulatory effect of adenosine. Guanosine, or guanine, cytidine, uridine, or thymidine nucleotides had no effect on the accumulation of cyclic AMP. Among other adenine nucleotides we tested, adenosine 5'-monophosphoramidate, but not adenosine 5'-monosulfate significantly increased cyclic AMP especially with the addition of papaverine. Neither 2'- nor 3'-adenylic acid were effective. Our data indicate that pig epidermis has four specific and independent adenylate cyclase systems for adenosine (and adenine nucleotides), histamine, epinephrine and prostaglandin E.
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PMID:Adenosine and adenine nucleotides stimulation of skin (epidermal) adenylate cyclase. 18 2

In a first series of experiments, the effects of uridine and inosine on glucose metabolism in rat diaphragm muscle incubated in Krebs-bicarbonate buffer were studied. Uridine in concentrations of 10(-4) to 10(-6) M stimulated the uptake of glucose and increased the content of glycogen, but had no effect on the production of lactate. When diaphragm muscles were incubated in the buffer without glucose, uridine (10(-4)-10(-6) M) had no effects on the content of glycogen and on the production of lactate. On the other hand, inosine in concentrations of 10(-4) to 10(-6) M stimulated the uptake of glucose and the production of lactate, but had no effect on the content of glycogen in the muscle. In a second series of experiments, uridine (10(-4)-10(-5) M) and inosine (10(-4)-10(-7) M) inhibited the relase of glycerol from isolated rat epididymal adipose tissue in Krebs-bicarbonate buffer. Uridine and inosine in concentrations of 10(-4) M inhibited the epinephrine (10(-5) M)-, the norepinephrine (10(-5) M)- and the theophylline (10(-3) M)-stimulated lipolysis. Dibutyryl 3',5'-adenosine monophosphate-stimulated lipolysis was further activated in the presence of 10(-4) M uridine or inosine. Dose-response curves studies suggested that inosine, but not uridine, has a common receptor site with epinephrine in adipose tissue. These results demonstrated that both nucleosides stimulated the glucose uptake, but only uridine increased the synthesis of glycogen in the muscle. Both nucleosides also inhibited lipolysis in adipose tissue. The mechanism of antilipolytic action of these nucleosides is unknown, but one of the receptor sites for inosine might be adenylate cyclase.
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PMID:Effects of uridine and inosine on glucose metabolism in skeletal muscle and activated lipolysis in adipose tissue. 18 86

Thyrotrophin (TSH) regulates the biosynthesis of thyroid protein and RNA. This action is mediated by adenylate cyclase and cycl AMP. In the present study the action of cyclic GMP and cyclic CMP was investigated in beef slices. Both cyclic AMP and cyclic GMP significantly increased the incorporation of [3H]uridine into RNA. These effects were blocked by actinomycin D, suggesting that their action is located at a preor at a transcriptional step. The PCA soluble fraction radioactivity followed in parallel with tha variations observed in the RNA fraction, supporting the view that cyclic nucleotides may regulate RNA by modulating the nucleotide precursors pool. Cyclic CMP in concentrations between 0.35 to 1.5 mM progressively decreased the RNA labelling, and the values of the PCA soluble radioactivity again followed those of RNA. Furthermore, cyclic CMP also blocked the in vitro stimulatory action of cyclic AMP on the incorporation of [3H]leucine into protein, and of [3H]uridine into RNA. The present results provide the first information on the action of cyclic AMP on RNA synthesis and suggest that negative signals may also play a part in the regulation of thyroid function.
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PMID:Action of cyclic nucleotides on protein and RNA synthesis in the thyroid. 18 48

Substrate uptake, portions of the cyclic AMP system, membrane fluidity and cellular phospholipid content are some of the parameters which are structurally associated with the plasma membrane and which have been linked to the control of cell proliferation. These parameters were studied with respect to cellular aging of human embryo lung fibroblasts (HELF) in culture. We observed in late passage an increase in the rate of uridine transport and in cellular cyclic AMP levels. These results were examined in relation to the increase in cell volume which occurs in senescing HELF. We also observed an increase in Vmax of uridine transport, and a decrease in the Km of cyclic AMP phosphodiesterase (PDE) as quiescent, passage 18-25, HELF were stimulated to divide with fresh serum. A similar effect of serum occurred in late passage (p. 43) cells despite the inability of these late passage cultures to undergo further proliferation. There was no change in cAMP-PDE activity with increasing passage number suggesting that the observed alterations of the cAMP levels, basal and in response to extracellular effectors, were due to alterations in the adenyl cyclase system. We observed no change in senescent HELF in membrane fluidity or phospholipid and neutral fat content.
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PMID:Plasma membrane associated metabolic parameters and the aging of human diploid fibroblasts. 20 16

Using tunicamycin, we have investigated the role of glycoproteins in membrane transport. Tunicamycin is a glucosamine-containing antibiotic that specifically inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues of glycoproteins. Inhibition of protein glycosylation in chick embryo fibroblasts by tunicamycin or other inhibitors of glycosylation resulted in defective transport of glucose, uridine, and amino acid analogs (alpha-aminoisobutyrate and cycloleucine). The defect in glucose transport is accompanied by decreased glucose metabolism, as determined by rates of CO2 and lactate production. In contrast, tunicamycin treatment did not affect other membrane-associated processes, such as secretion of fibronectin and procollagen, uptake of glucose by passive diffusion, Na+/K+ ATPase and adenylate cyclase activities, or stimulation of adenylate cyclase by prostaglandin and cholera toxin. Two glucose/glycosylation-regulated membrane proteins with apparent subunit molecular weights of 95,000 and 75,000 were induced by tunicamycin treatment. Our results indicate that glycoprotein glycosylation is required for membrane transport.
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PMID:Evidence for role of glycoprotein carbohydrates in membrane transport: specific inhibition by tunicamycin. 21 20

1. Intact mouse neuroblastoma NS20 cells, in the presence of cyclic adenosine 3':5'-monophosphate (cAMP) phosphodiesterase inhibitor, responded to adenosine (200 muM) and 2-chloroadenosine (200 muM) with a 20-fold increase in intracellular cAMP levels. AMP (200 muM) additions caused only a 3.5-fold cAMP level elevation. ATP, ADP, guanosine, cytidine, uridine, and guanine, all at 200 muM, had no effect on the cAMP level of these cells. 2. Homogenate NS20 adenylate cyclase activity was increased 2.5- to 4-fold by addition of 200 muM adenosine, 2-chloroadenosine, 2-hydroxyadenosine, or 8-methylaminoadenosine. Prostaglandin E1 additions (1.4 muM) produced about an 8-fold stimulation of homogenate cyclase activity. The Km of homogenate cyclase activation by adenosine and 2-chloroadenosine was 67.6 and 6.7 muM, respectively. Addition of 7-deazaadenosine, tolazoline, yohimbine, guanosine, cytosine, guanine, 2-deoxy-AMP, and adenine 9-beta-D-xylopyranoside, all at 200 muM were found to be without effect on homogenate NS20 adenylate cyclase. Two classes of inhibitors of homogenate NS20 adenylate cyclase activity were observed. One class, which included AMP, adenine, and theophylline, blocked 2-chloroadenosine but not prostaglandin E1 stimulation of cyclase. Theophylline was shown to be a competitive inhibitor of 2-chloroadenosine, with a Ki of 35 muM. The second class of inhibitors, which included 2'- and 5'-deoxyadenosine, inhibited unstimulated, 2-chloroadenosine and prostaglandin E1-stimulated homogenate cyclase activity to about the same degree. 3. Activation of NS20 homogenate adenylate cyclase by adenosine appears to be noncooperative. 4. The inhibitory action of putative "purinergic" neurotransmitters is postulated to be due to their effects on adenylate cyclase activity.
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PMID:Mouse neuroblastoma adenylate cyclase. Adenosine and adenosine analogues as potent effectors of adenylate cyclase activity. 117 Oct 95

Glucocorticoids secreted by the fetal adrenal, or administered for therapeutic reasons, stimulate fetal lung maturation in the human and other species. Prostacyclin, produced within the lung may be another agent with maturational effects. In this investigation we have demonstrated that glucocorticoids interact with lung cells and increase their response to a prostacyclin analogue (Iloprost, PGIp). This agent stimulates adenylate cyclase activity in fetal lung fibroblasts, fetal lung epithelial cells and in neonatal vascular smooth muscle cells. The cAMP response to PGIp in fibroblasts and epithelial cells occurred in the range 3nM-1 microM. When fibroblasts were pretreated with cortisol before PGIp, cAMP was increased 2-3 fold (p less than 0.01). There was a similar increase in cAMP after cortisol pretreatment in response to PGIp by fetal lung epithelial cells, but not with smooth muscle cells. The action of cortisol was blocked by an inhibitor of RNA synthesis (Actinomycin D) but not by an inhibitor of DNA synthesis (5-fluorodeoxy-uridine). Additional experiments with cholera and pertussis toxins, and with forskolin suggest that cortisol principally increases the quantity or activity of the adenylate cyclase sub-unit in fetal lung fibroblasts and, in doing so, increases the cAMP response to PGIp.
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PMID:Interaction between prostacyclin and cortisol in fetal lung cells: effects on cAMP production. 171 20

The metabolism of RNA has not been studied in the osteoclast (OC) because these bone-resorbing cells are only available in small numbers and cultures are always contaminated with other cells. Using two single-cell assay techniques, tritiated uridine (3H-UdR) autoradiography and gallocyanin quantitative cytophotometry, we have examined RNA synthesis in OCs isolated from neonatal rats. Oligo-nuclear OCs showed greater nuclear uptake of 3H-UdR than cells with many nuclei, and the variance of nuclear labeling within polykarya was greater in the latter, possibly because they contain nuclei of various ages. Salmon calcitonin (sCT) was a potent (ED50 approximately 5 x 10(-12) M) and rapid (40% reduction in 2 h, 75% reduction in 6 h) inhibitor of 3H-UdR uptake, and also reduced cytochemical total cellular RNA by 22% within 4 h. Forskolin (10(-5) M) inhibited nuclear uptake of 3H-UdR, suggesting that the sCT response may be mediated by cyclic AMP. Following a short (30 min) exposure to sCT, there was a progressive decline in labeling, followed by complete recovery by 4.5 h, a response possibly related to the phenomenon of calcitonin-induced persistent activation of adenylate cyclase. Inhibition of OC RNA synthesis may be an important component of its anti-resorptive action.
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PMID:RNA synthesis in isolated rat osteoclasts: inhibitory effect of calcitonin. 172 9

In order to obtain more insight into the possible role of cyclic AMP or cyclic GMP in modulating the initial cellular processes following activation of lymphocytes, we measured the effects of the T-cell mitogen concanavalin A and other substances including hormones on the cyclic nucleotide levels in human peripheral blood lymphocytes. The enzyme activities of the corresponding nucleotide cyclases, adenylate cyclase and guanylate cyclase were measured in both isolated plasma membranes or the cytosol of resting or concanavalin A stimulated rabbit thymocytes. Concanavalin A in a mitogenic concentration of about 5-10 micrograms/ml caused small, but consistent increases in cAMP but no changes in cGMP levels during the first hour of activation. Concomitantly, the specific activity of plasma membrane-bound adenylate cyclase was always increased at least 1.5-fold 30 min after stimulation of rabbit thymocytes with concanavalin A, but no effect could be detected on the specific activities of plasma membrane-bound or soluble guanylate cyclase. At high, supraoptimal concentrations of concanavalin A (more than 20 micrograms/ml) cAMP levels dramatically increased in human lymphocytes within minutes, but cGMP levels again were unaffected. Forskolin and beta-adrenergic hormones elevated cAMP in human lymphocytes, whereas cGMP levels were increased by the addition of sodium nitroprusside or alpha-adrenergic hormones. Sodium nitroprusside, in concentrations which elevated cGMP in human lymphocytes, had no influence on the incorporation of [3H]uridine into RNA of resting or concanavalin A stimulated human lymphocytes. Addition of forskolin resulted in an increase of cAMP levels and a dose-dependent decrease of [3H]uridine incorporation into RNA of concanavalin A-stimulated lymphocytes with no effect on resting lymphocytes. The data suggest that cGMP does not play a role in the initial phase of mitogenic activation of lymphocytes, whereas cAMP may be involved in the blast transformation process as an inhibitory signal.
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PMID:Are cyclic nucleotides involved in the initiation of mitogenic activation of human lymphocytes? 241 Dec 97


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