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)

Addition of adenosine (10-7 to 10-4 M) to the tear side of isolated corneas (Rana catesbeiana) produced a rapid, sustained increase in short-circuit current, potential difference, and radioisotopic chloride net flux. The increased net chloride flux accounted for the increased short-circuit current. Adenosine, a known activator of adenyl cyclase in other tissues, exerted its effects on chloride transport through a receptor different from the one described for epinephrine and prostaglandins in the corneal epithelium. Propranolol inhibited the epinephrine response but not the adenosine effect. Dipolyphloretin phosphate inhibited prostaglandin responses but did not affect the adenosine stimulation of chloride transport. Adenine and/or ribose, parts of the adenosine molecule, had no stimulatory effect, but 5'-AMP had a partial effect. The activation of the chloride pump with DBcAMP blocked the response to adenosine. Adenosine interacted with the effects of theophylline. Adenosine, a naturally occurring molecule, stimulated chloride transport by activation of adenyl cyclase through a separate membrane receptor in the corneal eqithelium.
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PMID:Action of adenosine on chloride active transport of isolated frog cornea. 31 16

The effect of adenosine in insulin secretion and adenylate cyclase activity of rat islets of Langerhans was investigated. Adenosine inhibited insulin secretion stimulated by glucose, glucagon, prostaglandin E2, tolbutamine and theophylline. Adenosine decreased basal adenylate cyclase activity of the islets as well as that stimulated by glucagon prostaglandin E2 and GTP, although fluoride-stimulated activity was not affected. Neither insulin secretion nor adenylate cyclase activity of the islets was affected by adenine, AMP or ADP. The inhibitory effect of adenosine on adenylate cyclase activity was not altered by either phenoxybenzamine (alpha-adrenergic blocker) or propranolol (beta-adrenergic blocker), suggesting that the effect is not mediated through the adrenergic receptors of the islet cells. These results suggest that the intracellular concentration of adenosine in the beta-cell may play a role in regulating insulin secretion and that this effect may be mediated via alterations in the activity of adenylate cyclase in the beta-cell.
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PMID:Adenosine and the regulation of insulin secretion by isolated rat islets of Langerhans. 32 13

Adenosine caused a dose-dependent stimulation of adenylate cyclase in homogenates from rat striatum and tuberculum olfactorium (200 and 300% stimulation by 100 muM adenosine). The effect of adenosine was not antagonized by haloperidol. Subcellular fractionation suggested that adenosine stimulates a different adenylate cyclase than dopamine. Basal adenylate cyclase activity in freshly prepared homogenates was reduced by dialysis and by the addition of adenosine deaminase. Basal adenylate cyclase activity was enchanced by papaverine and dipyridamole, but reduced by theophylline and isobutylmethylxanthine. The results are compatible with the opinion that endogenous adenosine is capable of activating adenylate cyclase in these areas of the rat brain.
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PMID:Activation of adenylate cyclase from rat striatum and tuberculum olfactorium by adenosine. 59 2

Incubation of bovine adrenocortical membranes with corticotropin and 5-guanylylimidodiphosphate produced a state of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) with maximal catalytic activity and an increased sensitivity to inhibition by adenosine. Due to metabolism of adenine nucleotides during adenylate cyclase assays a quantitative assessment of the nature of this inhibition was not possible. However, when determined at 0.2--1.0 mM MgATP2-, half-maximal inhibition of the basal and maximally active states of the enzyme was observed at adenosine concentrations of 210--330 and 70--90 micrometer, respectively. The inhibition appeared to be partially competitive, suggesting that the nucleoside may act as an allosteric negative effector which reduces the affinity of the active site for substrate. Adenosine was 5--6 times more potent as an inhibitor of adrenal adenylate cyclase than 2-chloroadenosine. Adenosine deaminase abolished the inhibitory effect of the nucleoside, whilst theophylline had no effect on activity either in the absence or presence of adenosine.
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PMID:Inhibition of bovine adrenocortical adenylate cyclase activity by adenosine. 71 50

Characteristics of adenylate cyclase activity of the intima plus media layer of pig coronary arteries have been studied. Enzyme activity in the 10,000 xg particulate fraction was linear with respect to time and protein during short incubations. Linear kinetics were observed for MgATP as a substrate and free Mg2+ as an activator. Mn2+ added in excess of ATP concentrations was only slightly stimulatory or inhibitory. Adenosine, GTP and GPP(N)P inhibited enzyme activity. Adenosine decreased the Vmax and the Ka for Mg2+ but had no effect on the Km for MgATP. The inhibition by adenosine was reversible, while that by GPP(N)P appeared to be irreversible. Although preincubation of the enzyme with GPP(N)P for short times caused irreversible inhibition, preincubation for more than 15 min caused up to 3-fold activation. Isoproterenol added to the incubation produced no or very slight stimulation with or without GPP(N)P or GTP, and preincubation with isoproterenol alone caused irreversible inhibition. However, preincubation with isoproterenol plus GPP(N)P for 30 min caused irreversible activation exceeding that observed with GPP(N)P alone. These observations suggest that vascular adenylate cyclase, like the enzyme from the other tissues, can exist in multiple states of activity and responsiveness.
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PMID:Characteristics of adenylate cyclase activity in pig coronary arteries. 72 77

Rat liver plasma membranes are shown to catalyze the formation of adenosine 5'-phosphoroglycerol and adenosine 5'-phosphoromethanol from ATP and glycerol or methanol, respectively. In the presence of 2.7 M glycerol and 1 mM ATP, 30 nmol of adenosine 5'-phosphoroglycerol were formed in 10 min per mg of rat liver plasma membranes. The structures of these phosphodiesters were determined from the following evidence. Radioactivity was incorporated into the nucleotide from [alpha-32P]ATP, [2,8-3H]ATP, or [2-3H]glycerol. Treatment with snake venom phosphodiesterase I converted the nucleotides to AMP. The compound formed from glycerol and ATP co-migrated with adenosine 5'-phosphoroglycerol synthesized from glycerol and adenosine 5'-phosphoromorpholidate in five thin layer chromatography systems. The methyl derivative co-migrated with adenosine 5'-phosphoromethanol synthesized from methanol and adenosine 5'-phosphormorpholidate in several thin layer chromatography systems. The synthesis of these phosphodiesters was also catalyzed by chicken embryo fibroblast membranes and solubilized rat liver plasma membranes but not by rat heart plasma membrane preparations. Formation of significant amounts of these phosphodiesters required relatively high concentrations of the alcohols (greater than 1 M). The alcohol concentration dependence did not exhibit substrate saturation at physiologically meaningful concentrations of glycerol or methacol. It is proposed that either the alcohols examined were not the natural substrates for this enzyme or that the alcohol/AMP phosphodiesters were formed as a result of trapping of an enzyme/nucleotide intermediate. Adenosine 5'-phosphoroglycerol formation was inhibited approximately 50% by 15 mM NaF. Epinephrine, norepinephrine, glucagon, and prostaglandin E1 were without effect. Alloxan, an inhibitor of adenylate cyclase did not inhibit formation of adenosine 5'-phosphoroglycerol. It is concluded that adenylate cyclase was not responsible for formation of these phosphodiesters. The physiological significance of this reaction remains undefined.
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PMID:Formation of adenosine 5'-phosphoroglycerol from ATP and glycerol by rat liver plasma membranes. 83 37

Adenosine inhibits the rat liver adenylate cyclase system at a regulatory site that is distinct from the glucagon receptor, the guanine nucleotide regulatory site, and the active site involved in catalysis of ATP to cyclic AMP. The effects of the nucleoside are also independent of the concentration of uncomplexed ATP (ATP4-) in the assay medium. Glucagon, but not guanine nucleotides, sensitizes the system to inhibition by adenosine. Depending on assay conditions, the hormone can shift the concentration of adenosine required for 50% inhibition by as much as 10-fold. Under optimal conditions, the apparent Ki for adenosine is 25 micron. Both Mg2+ and Mn2+ increase adenylate cyclase activity and, in order of relative potency, increase the sensitivity of the enzyme to adenosine inhibition; Mn2+ is 50- to 100-fold more potent than Mg2+. The adenosine inhibitory site exhibits stringent structural requirements for nucleoside action. Most alterations of the purine ring result in loss of activity, whereas alterations in the ribose ring are tolerated, and some deoxyadenosine analogs are even more effective than adenosine. Naturally occurring nucleosides and nucleotides, such as inosine, guanosine, and 5'-AMP, are inactive. Analog studies reveal also that inhibition of the hepatic system occurs at a site which is clearly different from the sites through which adenosine activates other adenylate cyclase systems, and that the liver enzyme appears to have no site for activation by the nucleoside.
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PMID:Regulation by glucagon and divalent cations of inhibition of hepatic adenylate cyclase by adenosine. 89 90

Broken cell particulate preparations of adenylate cyclase isolated from the human glioma cell line 132-1N1 were stimulated 2-to 3-fold by 30 muM adenosine. This concentration of adenosine produced a maximal stimulation of the cyclase while 3 to 5 muM adenosine produced half-maximal stimulation. Theophylline, at 40 muM, inhibited the adenosine stimulation of the adenylate cyclase by about 40% while 200 muM produced near complete inhibition. The inhibition by theophylline could be overcome by increasing adenosine to a concentration 10-fold that of theophylline, implying that the inhibition was competitive. Basal activity was not inhibited by even 1.0 mM theophylline, nor was the epinephrine stimulated activity. In contrast, 1.0 muM propranolol essentially completely inhibited the 8-fold stimulation of 1.0 muM epinephrine but had no effect on either basal or adenosine-stimulated activity. Adenosine and 2-chloroadenosine were equipotent in stimulating adenylate cyclase from the 132-1N1 line, whereas neither adenine nor guanosine had any detectable effect. GTP, 10 muM, produced a small variable stimulation of the adenylate cyclase while the GTP analogue, 5'-guanylylimidodiphosphate (Gpp(NH)p), produced a marked stimulation fo the cyclase. Preincubation of the adenylate cyclase preparation with the analogue greatly increased its potency and maximal effect. In contrast, both basal and adenosine-stimulated activity decreased markedly with preincubation. The effects of adenosine or epinephrine in combination with Gpp(NH)p were at least additive and often synergistic in comparison to the effects of the compounds alone. The effects of adenosine on intact and broken cell preparations of the human fibroblast lines WI-38 and VA13-2RA were also examined. In the intact VA13-2RA, adenosine produced rapid and large increases in intracellular and extracellular cyclic adenosine 3':5'-monophosphate (cAMP). In the parental fibroblast line, the WI-38, adenosine slightly elevated basal levels of cAMP, but only produced marked elevations in the presence of non-methylxanthine phosphodiesterase inhibitors. The effect of adenosine on the broken cell particulate preparations of adenylate cyclase from the fibroblasts was similar to its action on the cyclase from the 132-1N1; 30 muM adenosine produced a maximal stimulation of the adenylate cyclase, and the stimulation was inhibited by theophylline.
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PMID:Regulation of adenylate cyclase from cultured human cell lines by adenosine. 93 31

The cervicovaginal epithelium of neonatal mice produces a material with specific antigenic properties (CVA) and this material is produced in increased amounts after estradiol treatment. Using a cytochemical method, estradiol treatment was shown to result in an increase of adenylate cyclase activity in the same epithelium. When d-propranolol is injected together with estradiol, the increase in CVA is inhibited, while the hormone-induced proliferation of epithelial cells is not influenced. When adenylate cyclase activity is studied under identical conditions, the estradiol-promoted increase in enzyme activity is largely counteracted by d-propranolol. These findings would suggest that Adenosine 3"5"-cyclic monophosphate (cAMP) has a role in some, but not all, estradiol-mediated effects in the neonatal cervicovaginal epithelium.
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PMID:Effects of d-propranolol and estradiol on the cervicovaginal epithelium. 99 Dec 44

The involvement of guanine-nucleotide-binding proteins (G-proteins) and regulation of cyclic AMP (cAMP) in interleukin 1 (IL1) signal transduction has been investigated in EL4 and 7OZ/3 cells expressing Type 1 and Type 2 IL1 receptors respectively. Results show that in both cell types IL1 alone failed to induce changes in cellular cAMP levels, and in membrane preparations the cytokine had no significant effect on adenylate cyclase activity. In contrast, forskolin stimulated cAMP levels in cells and membranes. IL1 did not significantly alter GTPase activity or rate of guanosine 5'-[gamma-[35S]thio]triphosphate binding measured in membrane preparations from the EL4 and 7OZ/3 cells. In EL4-cell membrane preparations the kinetics of 125I-IL1 binding were altered in the presence of guanosine 5'-[beta gamma-imido]triphosphate, resulting in the formation of a higher-affinity state for IL1 binding. Adenosine 5'-[beta gamma-imido]triphosphate at the same concentration was without effect. These results suggest that IL1 receptor function may be regulated by guanine nucleotides; however, the mechanism appears to differ from that exhibited by conventional G-protein-linked receptors. The lack of significant effects of IL1 on cAMP metabolism in these cells suggests that alternative pathways must exist to mediate the intracellular responses to stimulation via both types of the IL1 receptor.
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PMID:Investigation of guanine-nucleotide-binding protein involvement and regulation of cyclic AMP metabolism in interleukin 1 signal transduction. 131 61


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