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)

The properties of adenylate cyclase from bovine and human corneal epithelium were investigated. Adrenergic drugs were the most effective stimulatory agents tested in bovine tissue, causing greater activation than did fluoride. Isoproterenol was the most potent agonist, followed by epinephrine and norepinephrine. Phenylephrine and dopamine also stimulated adenylate cyclase through beta-adrenergic receptors at relatively high concentrations. Enzyme stimulation by all the adrenergic drugs tested was completely inhibited by 1 microM propranolol or 0.1 microM timolol. The GTP analogue, GppNp, produced considerable activation and caused an augmented response when combined with isoproterenol, but not with fluoride. Prostaglandins E1, E2, or F2 alpha produced a small but significant stimulation over control which was not sensitive to propranolol inhibition. Adenylate cyclase from human corneal epithelium exhibited qualitatively similar characteristics to those of the bovine enzyme. Fluoride was the most effective stimulatory agent, followed by isoproterenol, phenylephrine, and dopamine. Prostaglandins failed to stimulate adenylate cyclase activity in human corneal epithelial preparations.
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PMID:Characterization of adenylate cyclase activity in bovine and human corneal epithelium. 610 5

Fluoride and peptide-stimulated adenylate cyclase activity was investigated by electron histochemistry on serial sections of the RPAI neuron of the snail Helix pomatia. Fluoride-stimulated adenylate cyclase was detected in the surface membrane of the RPAI neuron, the postsynaptic membrane of axosomatic contacts, and the surface of glial cells forming a multilayer capsule around the neuron. Peptide-stimulated adenylate cyclase was located in the membrane of glial cells surrounding the neuron, their processes (trophospongia) invaginating deeply in the neuronal soma, and the membrane of somatic protrusions forming the system of lacoons in the region of the axosomatic contact. No peptide-stimulated adenylate cyclase was revealed in the remaining part of the surface of the somatic membrane. The localization of adenylate cyclase activity in the postsynaptic membrane in the region of the axosomatic contact is in accordance with the hypothesis based on electrophysiological experiments that the cyclase system participates in the genesis and regulation of the bursting activity of the RPAI neuron.
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PMID:The axosomatic contacts on the bursting neuron of the snail Helix pomatia. II. Ultrastructural localization of adenylate cyclase. 620 58

Female Sprague-Dawley rats were subjected to endurance-training programs, and the effect of training on myocardial beta-adrenergic receptor number, receptor-binding characteristics, and adenylate cyclase (AC) activities associated with the receptor were examined. Training produced a 45% (P less than 0.01) increase in the succinate dehydrogenase activity of the plantaris muscle. Specific (-)-[3H]dihydroalprenolol (DHA)-binding data were subjected to Scatchard plot analysis to quantify beta-adrenergic receptor number and DHA-binding characteristics of myocardial membranes. The DHA concentrations at which 50% of the total binding sites were occupied were similar for membranes from sedentary (1.95 +/- 0.51) and trained (1.59 +/- 0.34 nM) groups. Total DHA-binding sites of membranes from control (91.6 +/- 13.3) and trained (83.1 +/- 7.6 fmol/mg) groups were also similar. Basal and maximally stimulated AC activities were also unchanged by endurance training. Fluoride-stimulated AC activities of crude homogenate and 10,000 g fractions decreased 47 and 49%, respectively, with training. No differences were observed in a 40,000 g fraction. The specific activities of a ouabain-sensitive Na+-K+-ATPase (a sarcolemmal membrane marker) of crude homogenate, 10,000 g, and 40,000 g membrane fractions were similar. These data indicate that training produces no detectable difference in the potential for adrenergic responses at the receptor level.
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PMID:Effect of training on beta-adrenergic receptor number in rat heart. 628 86

Ca2+ decreased the lipid fluidity of rat liver plasma membranes labeled with 5-nitroxide stearate, I(12,3), as indicated by the order parameter (S). These effects form a reversible, saturable process with an association constant of 1 x 10(3) M-1. Arrhenius-type plots of S indicated that the lipid phase separation, present in the external leaflet of native membranes between 28 and 19 degrees C, is perturbed by mM Ca2+ such that the high temperature onset is elevated to 32-34 degrees C. Fluoride-stimulated adenylate cyclase was similarly inhibited by Ca2+ (ID50 = 1 mM) for the enzyme in membrane-bound or solubilized states. The glucagon-stimulated activity was more sensitive to Ca2+ inhibition with an ID50 of 0.2 mM. These inhibitory effects are due neither to perturbations of glucagon binding to its receptor nor to fluidity changes, but are instead attributed to direct Ca2+-enzyme interactions. Such binding desensitizes the enzyme to fluidity alterations induced by temperature elevation or benzyl alcohol addition. With Ca2+, Arrhenius plots of glucagon-stimulated activity indicated breaks at 32 and 16 degrees C, whereas those of fluoride-stimulated activity showed one break at 17 degrees C. Without Ca2+, Arrhenius plots exhibited one break at 28 degrees C for glucagon-stimulated activity, whereas fluoride-stimulated plots were linear. We propose that Ca2+ achieves these effects through asymmetric perturbations of the membrane lipid structure.
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PMID:Perturbations of liver plasma membranes induced by Ca2+ are detected using a fatty acid spin label and adenylate cyclase as membrane probes. 629 44

The inhibitory and stimulatory guanine nucleotide-binding regulatory components (Gi and Gs) of adenylate cyclase both have an alpha X beta subunit structure, and the beta (35,000 Da) subunits are functionally indistinguishable. Gi and Gs both dissociate in the presence of guanine nucleotide analogs or Al3+, Mg2+, and F- in detergent-containing solutions. Several characteristics of Gi- and Gs-mediated regulation of adenylate cyclase activity have been studied in human platelet membranes. The nonhydrolyzable analog of GTP, guanosine-5'-(3-O-thio)triphosphate (GTP gamma S) mimics GTP-dependent hormonal inhibition or stimulation of adenylate cyclase under appropriate conditions. This inhibition or stimulation follows a lag period. The combined addition of epinephrine or prostaglandin E1 with GTP gamma S results in the immediate onset of steady state inhibition or activation. The effects of the GTP analog are essentially irreversible. Fluoride is also an effective inhibitor of prostaglandin E1-stimulated adenylate cyclase, while it markedly stimulates the basal activity of the enzyme. The addition of the resolved 35,000-Da subunit of Gi to membranes results in inhibition of adenylate cyclase, and the resolved 41,000-Da subunit has a stimulatory effect on enzymatic activity. The inhibitory action of the 35,000-Da subunit is almost completely abolished in membranes that have been irreversibly inhibited by GTP gamma S plus epinephrine; this irreversible inhibition is almost completely relieved by the 41,000-Da subunit. Detergent extracts of membranes that have been treated with GTP gamma S plus epinephrine contain free 35,000-Da subunit. The 41,000-Da subunit of Gi contained in such extracts has a reduced ability to be ADP-ribosylated by islet-activating protein (IAP), which implies that this subunit is in the GTP gamma S-bound form. The irreversible inhibition of adenylate cyclase caused by GTP gamma S (plus epinephrine) in membranes is highly correlated with the liberation of free 35,000-Da subunit activity and is inversely related to the 41,000-Da IAP substrate activity in detergent extracts prepared therefrom. The increase in free 35,000-Da subunit activity in extracts and the inhibition of adenylate cyclase activity in GTP gamma S (plus epinephrine)-treated membranes are both markedly inhibited by treatment with IAP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Subunit dissociation and guanine nucleotide-dependent hormonal inhibition. 632 31

Trypsin, chymotrypsin, and papain stimulate basal adenylate cyclase activity in bovine thyroid plasma membranes in a dose-related, albeit biphasic, fashion. Each of the proteases enhanced TSH-stimulated adenylate cyclase activity over basal activity. The proteases also enhanced GTP-, guanosine 5'-(beta, gamma-imidotriphosphate)-, prostaglandin E1-, and cholera toxin-stimulated adenylate cyclase to varying degrees. Fluoride-stimulated activity was enhanced by chymotrypsin and papain, but not by trypsin. When Mn++ was substituted for Mg++ in the adenylate cyclase assay, no stimulation by the proteases were observed. To see if endogenous membrane proteases are required for optimal thyroid adenylate cyclase response to TSH and other stimulators, studies were performed using the protease inhibitors tosylamide 2-phenylethyl-chloromethyl ketone (TPCK) and p-tosyl-L-arginine methyl ester (TAME), inhibitors of chymotrypsin and trypsin, respectively. TPCK (0.15 mM) had no effect on basal adenylate cyclase activity, but did inhibit TSH-, trypsin-, and chymotrypsin-stimulated activities by approximately 90%. Guanosine 5'-(beta, gamma-imido) triphosphate- as well as cholera toxin-stimulated activities were inhibited by approximately 50%, whereas prostaglandin E1- and fluoride-stimulated activities were inhibited by approximately 25%. TAME (6 mM) produced similar results, except that no effect on fluoride activity was seen, while basal activity was inhibited by approximately 20%. Thus, various serine proteases augment both basal and hormone-stimulated adenylate cyclase in bovine thyroid. Since both trypsin- and chymotrypsin-stimulated as well as TSH-induced enzyme activities were inhibited by TPCK and TAME, it would appear that augmentation of thyroid adenylate cyclase activity may, in part, result from stimulation of endogenous proteases.
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PMID:Effects of proteolytic enzymes and protease inhibitors on bovine thyroid adenylate cyclase activity. 633 11

Forskolin is an activator of adenylate cyclase in many cell types. In order to determine the mechanism of forskolin's action and to determine if this mechanism is shared by hormones and other agonists of the adenylate cyclase system, we isolated and partially characterized several spontaneous, forskolin-resistant mutants from the Y1 mouse adrenocortical tumor cell line. Forskolin increased adenylate cyclase activity in Y1 cell homogenates approximately 30-fold. By virtue of its effect on cAMP accumulation, forskolin (10 microM) also inhibited the growth of Y1 cells in monolayer culture. Using forskolin as a selective agent, spontaneous mutants capable of growth in the presence of 10 microM forskolin were isolated from the Y1 cell line at a frequency of 1-2/10(6) cells. In these mutants, resistance was stable, resulting from a defect in cAMP accumulation rather than cAMP action, and was associated with a reduced ability of forskolin to stimulate adenylate cyclase activity in cell homogenates. Whereas corticotropin stimulated adenylate cyclase activity over 35-fold in cell homogenates from the Y1 parent, ACTH had only marginal effects on the enzyme's activity in the mutant clones. Fluoride-stimulated adenylate cyclase activity seemed unimpaired. These results suggest that the resistance to forskolin resulted from a mutation in the adenylate cyclase system, not in the catalytic subunit, but at a locus related to the ACTH.
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PMID:Isolation of forskolin-resistant adrenal cells defective in the adenylate cyclase system. 653 78

The mechanism by which chloride stimulates adenylate cyclase was investigated. Depletion of GDP increased basal adenylate cyclase activity and reduced the stimulation by isoprenaline. Restoration of bound GDP partially reversed these effects. Chloride stimulated cyclase activity by the same proportion in control, GDP-depleted and GDP-restored preparations, as did Gpp(NH)p. Fluoride increased adenylate cyclase activity to the same final level in both GDP-depleted and GDP-restored membranes; addition of Gpp(NH)p as well as fluoride had no further effect. Solubilisation of adenylate cyclase reduced the stimulatory effect of Gpp(NH)p only slightly, but greatly attenuated the activation by chloride. We conclude that chloride does not stimulate cyclase activity by an action on GDP exchange. Activation by chloride may be due to a disrupting or chaotropic effect on membrane/protein interactions.
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PMID:The mode of action of chloride on rabbit heart adenylate cyclase. 670 95

Fluoride activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] is significantly enhanced (2 to 5 times) by a protein factor isolated from rat brain. The fluoride-dependent adenylate cyclase stimulator (FCS) is nondialyzable, trypsin-labile, and stable at 90 degrees C for 10 min. FCS stimulates adenylate cyclase activity only in the presence of NaF (2-25 mM) and this effect is independent of added GTP, 5'-guanylylimidodiphosphate, or calcium. FCS has been purified roughly 3000-fold from a 12,000 X g supernatant fraction of rat brain homogenate. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis and sucrose density gradient sedimentation suggest that FCS is a monomer with an apparent Mr of 59,000. Isoelectric focusing indicates FCS has a pI of 8.9. FCS from rat brain stimulates fluoride-activated adenylate cyclase from a variety of cell types, and FCS can also be isolated from rat liver. The effects of FCS are not reversed by washing membranes when the membranes and FCS are preincubated with NaF. The Km of adenylate cyclase for ATP and the fluoride concentration causing half-maximal activation are unchanged by FCS; however, FCS increases the Vmax by 2.5-fold. FCS may act to increase the catalytic efficiency of fluoride-activated complexes of the GTP-binding unit with adenylate cyclase or to enhance the formation of additional active complexes.
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PMID:Partial purification and characterization of a macromolecule which enhances fluoride activation of adenylate cyclase. 693 10

An LH sensitive adenylate cyclase from a tumour Leydig cell has been investigated. The plasma membranes, prepared by a 2 phase (dextran-polyethylene glycol) centrifugation method were found to have the following properties: In the presence of LH plus p(NH)ppG (guanosine 5'-beta, gamma-imido triphosphate) or fluoride ions, maximum adenylate cyclase activity was obtained in the plasma membranes with 4 to 6 mM Mg2+ plus 0.33 to 2 mM ATP. LH alone stimulated adenylate cyclase activity 2-fold when compared with basal activity and the time course of cyclic AMP production was linear up to 45 min. With GTP (10(-5)M) and GTP plus LH, adenylate cyclase activity was increased 3 and 6-fold, respectively, for up to 20 min and thereafter declined. In contrast p(NH)ppG (10(-5)M) and p(NH)ppG plus LH increased adenylate cyclase activity 7 and 14-fold which was maintained for at least 45 min. Fluoride ions increased the enzyme activity linearly over 45 min approx 18-fold. When GTP or p(NH)ppG were added alone there was a lag time of activation of approximately 10 min which was abolished by the addition of LH. GTP but not p(NH)ppG at concentrations greater than 10(-4) inhibited basal and LH stimulated adenylate cyclase when compared with 10(-5)M GTP. The tumour Leydig cell adenylate cyclase is thus essentially similar to other hormone sensitive somatic cells. The present study makes it feasible to prepare plasma membranes by a simple method from large quantities of pure Leydig cells.
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PMID:Isolation and characterization of plasma membranes containing LH sensitive adenylate cyclase from a Leydig cell tumour. 716 Sep 20


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