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 regulation of dopamine biosynthesis in tuberoinfundibular dopaminergic (TIDA) neurons by adenosine 3',5'-cyclic monophosphate (cAMP) was investigated in the present study. Dopamine biosynthesis in TIDA neurons was estimated by the rate of in vitro dihydroxyphenylalanine (DOPA) accumulation in the median eminence of rat hypothalamic slices after incubation with a DOPA decarboxylase inhibitor. Addition of dibutyryl cAMP (db-cAMP) into medium caused an increase in the rate of DOPA accumulation in the median eminence in a dose- and time-dependent manner. 8-Bromo-cAMP also increased the rate of DOPA accumulation in the median eminence and cAMP was less effective than db-cAMP whereas neither adenosine nor sodium butyrate altered the rate of DOPA accumulation. An increase in the concentration of endogenous cAMP achieved by addition into medium of isobutylmethylxanthine, a phosphodiesterase inhibitor, or forskolin, an adenylate cyclase activator, was associated with an increase in the rate of DOPA accumulation in the medium eminence. db-cAMP, however, had an almost negligible effect on the secretion of dopamine from the median eminence. The stimulatory effect of db-cAMP on DOPA accumulation in the median eminence was not dependent upon the presence of extracellular Ca2+ and was not blocked by tetrodotoxin. Furthermore, the stimulation of DOPA accumulation in the median eminence induced by db-cAMP was additive with that induced by high potassium depolarization, which was Ca2+ -dependent. These results suggest that dopamine biosynthesis in TIDA neurons is regulated by two distinct mechanisms, one of which involves cAMP, and another of which involves Ca2+.
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PMID:Adenosine 3',5'-cyclic monophosphate stimulates dopamine biosynthesis in the median eminence of rat hypothalamic slices. 242 58

Our previous work demonstrated that 8-bromo-cAMP promotes the secretion of both hCG and progesterone by cultured cytotrophoblasts. This study was conducted to characterize the adenylate cyclase of cytotrophoblasts and to examine the effects of agents that stimulate adenylate cyclase on hCG secretion. Adenylate cyclase activity was detected in purified cytotrophoblasts, as were membrane-bound stimulatory and inhibitory guanine nucleotide regulatory proteins, Gs and Gi. Adenylate cyclase was stimulated by MnCl2 and MgCl2, and the effects of MgCl2 were amplified by the GTP analog guanylylimidodiphosphate. Cholera toxin stimulated both cAMP and hCG production by cultured cytotrophoblasts, confirming the coupling of Gs to the adenylate cyclase. Forskolin also stimulated adenylate cyclase, cAMP synthesis, and hCG secretion. Pertussis toxin did not affect hCG secretion in either the absence or presence of forskolin. 8-Bromo-cAMP stimulated cytotrophoblast protein kinase activity, resulting in the increased phosphorylation of a protein with a mol wt of about 70,000, and produced a marked stimulation of hCG secretion. Our findings suggest that the level of expression of adenylate cyclase activity is one determinant of the endocrine function of the differentiating trophoblast.
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PMID:Adenylate cyclase in human cytotrophoblasts: characterization and its role in modulating human chorionic gonadotropin secretion. 244 28

1. Secretion of [3H]acetylcholine was studied in the guinea-pig ileum longitudinal muscle-myenteric plexus preparation. The transmitter stores of the cholinergic nerves were labelled by pre-incubation with [3H]choline. The preparation was mounted in an organ bath and superfused with Tyrode solution containing hemicholinium-3 and eserine. [3H]Acetylcholine secretion was evoked by electrical stimulation (0.5 Hz, 150 shocks). 2. 8-Bromo cyclic AMP, the adenylate cyclase activator forskolin, and the cyclic nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine enhanced the [3H]acetylcholine secretion in a concentration-dependent manner. The values of 'maximal enhancement' calculated were similar, viz. 200-300% of control. 3. 8-Bromo cyclic GMP reduced the [3H]acetylcholine secretion. 4. The 'maximal enhancement' of 3-isobutyl-1-methylxanthine was not altered by the presence of forskolin (25 mumol/l) suggesting a common mechanism of action, i.e. elevation of endogenous cyclic AMP levels. 5. The muscarinic acetylcholine receptor antagonist atropine enhanced the [3H]acetylcholine secretion with a 'maximal enhancement' of 506% of control. Presence of neither forskolin (25 mumol/l) nor 3-isobutyl-1-methylxanthine (5 mmol/l) altered the 'maximal enhancement' for atropine. 6. In contrast, atropine (1 mumol/l) and 4-aminopyridine (0.5 mmol/l) additively enhanced the [3H]acetylcholine secretion. 7. The results suggest that neuronal cyclic AMP may be involved in muscarinic acetylcholine receptor-mediated control of [3H]acetylcholine secretion in guinea-pig ileum myenteric plexus.
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PMID:Interaction of forskolin with the effect of atropine on [3H]acetylcholine secretion in guinea-pig ileum myenteric plexus. 245 81

We have characterized the effects of eight different drugs on the IgE-mediated histamine release (HR) and leukotriene C4 (LTC4R) from human basophils. Arachidonic acid analogues 5,8,11 eicosatriynoic acid and 5,8,11,15 eicosatetraynoic acid inhibit the release of both mediators in the range 10(-6) to 10(-4) mol/L with almost total (80% to 100%) inhibition of release at 10(4) mol/L. The inhibition of LTC4R was significantly (p less than 0.05) greater than the inhibition of HR only at intermediate (10(-5) to 3 X 10(-5) mol/L) doses of the drugs. Two other inhibitors of phospholipase A2 (bromophenacyl bromide and phenidone) affected the release of both mediators equally. Two drugs that activate adenylate cyclase (prostaglandin E1 and dimaprit) inhibited release in a dose-dependent fashion but failed to preferentially affect either HR or LTC4R. Isoproterenol (10(-6) to 10(-4) mol/L), a third activator of adenylate cyclase, caused only moderate (30%) inhibition of HR, even when the reaction was staged, but was slightly (0.1 less than p less than 0.05) more potent against leukotriene release. The final drug tested was the phosphodiesterase inhibitor, isobutylmethylxanthine, which proved to be an effective (50% to 100%) inhibitor of both mediators in the range 10(-5) to 10(-3) mol/L.
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PMID:The pharmacologic modulation of mediator release from human basophils. 245 75

Exposure of cultured hepatocytes to glucagon leads to a partial refractoriness of the adenylate cyclase both to glucagon (homologous desensitization) and to isoproterenol (heterologous desensitization). In contrast, isoproterenol produces a very strong homologous desensitization but almost no heterologous desensitization. The present study compared the pattern of the homologous and heterologous components of glucagon-induced desensitization in these cells, particularly during the first 4 hours, and examined the role of cyclic 3',5'-adenosine monophosphate (cAMP) in the mechanism of refractoriness development. The decrease in glucagon-sensitive and isoproterenol-sensitive adenylate cyclase activities were closely parallel with respect to the extent, the time course and the dose required. 8-Bromoadenosine 3',5'-monophosphate (8-Bromo-cAMP) also reduced the hormone-responsive adenylate cyclase activity, but this effect developed more slowly than the desensitization after glucagon treatment. No consistent relationship was found between cAMP levels and induction of hormone refractoriness when the cells were exposed to glucagon, isoproterenol, cholera toxin or forskolin. Furthermore, addition of 0.5 mM 3-isobutyl-1-methylxanthine) (IBMX) which strongly amplified the cAMP response, did not potentiate the glucagon-induced desensitization of either glucagon-sensitive or isoproterenol-sensitive adenylate cyclase activity. Taken together, the results suggest that homologous and heterologous desensitization of the adenylate cyclase developing after glucagon exposure occur by similar (agonist-non-specific) mechanisms which do not involve cAMP.
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PMID:Glucagon-induced refractoriness of hepatocyte adenylate cyclase: comparison of homologous and heterologous components and evidence against a role of cAMP. 247 64

The possible involvement of three different second-messenger systems, namely cyclic AMP/protein kinase (PK)-A, cyclic GMP/PK-G, and diacylglycerol (DG)/PK-C systems, in the perivascular nerve terminals of guinea pig mesenteric artery was examined by intracellular microelectrode recording. Excitatory junction potentials (EJPs) were evoked by perivascular nerve stimulation. Isoproterenol (0.1 microM) enhanced the EJP amplitude without modifying the passive membrane properties of the vascular smooth muscle (VSM) cells. The facilitatory effect of isoproterenol on EJP amplitude was completely abolished by beta-adrenergic blockade (0.3 microM propranolol). Forskolin (activator of adenylate cyclase) also augmented the EJP amplitude in a concentration-dependent manner (EC50 congruent to 10 microM), without affecting the passive membrane properties of the VSM cells. In addition, forskolin (1-10 mM) markedly potentiated the isoproterenol-induced stimulation of EJP amplitude (EC50 congruent to 2 microM). A permeant analogue of cyclic AMP, 8-bromo-cyclic AMP (0.1 and 1 mM), enhanced the EJP amplitude, thus mimicking the effects of isoproterenol and forskolin. 8-Bromo-cyclic AMP had no effect on the resting potential or current-voltage relationship of the VSM cells, thus suggesting that the membrane properties of the VSM cells were not altered. 8-Bromo-cyclic GMP (1 mM) also augmented the EJP amplitude, but its facilitatory effect was weaker than that of 8-bromo-cyclic AMP. 8-Bromo-cyclic GMP hyperpolarized the VSM membrane by 4 mV and decreased the input resistance, presumably due to an increase in K+ conductance. Phorbol-12-myristate-13-acetate (PMA, 30-300 nM), a direct activator of PK-C, significantly enhanced the EJP amplitude after 40 min in a concentration-dependent manner, without affecting the resting potential of the VSM cells. From these results, we suggest that cyclic AMP/PK-A, cyclic GMP/PK-G, and DG/PK-C systems might be involved in regulation of the release of neurotransmitter in the perivascular nerve terminals. However, the possibility of some action on the postsynaptic VSM cell cannot be excluded.
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PMID:Cyclic nucleotide regulation of neurotransmission in guinea pig mesenteric artery. 248 77

The structural organization of the low molecular mass form (43 kDa) of Bordetella pertussis adenylate cyclase was dissected taking advantage of the known sequence of the bacterial cya gene (Glaser, P., Ladant, D., Sezer, O., Pichot, F., Ullmann, A., and Danchin, A. (1988) Mol. Microbiol. 2, 19-30) and its low content of Trp and Met residues. Cleavage of the 43-kDa protein and of its complementary tryptic fragments (T25 and T18 peptides) with N-chlorosuccinimide and cyanogen bromide followed by sodium dodecyl sulfate-polyacrylamide gel analysis of digestion products allowed the following conclusions: (i) the catalytically active 43-kDa form of B. pertussis adenylate cyclase is within the first 400 residues of the protein encoded by the cya gene. T25 occupies the N-terminal domain of the protein (residues 1-235/237). Isolated T25 fragment exhibits a low but measurable enzymatic activity which indicates that it harbors the catalytic site; (ii) T18 which is the main calmodulin-binding domain, occupies the C-terminal segment of protein (residues 236/238-399) and is devoid of catalytic properties; (iii) the two complementary peptides T25 and T18 reassociated only in the presence of calmodulin, leading to significant recovery of the original activity. These results demonstrate that both fragments of the 43-kDa form of adenylate cyclase are essential for a high level of enzymatic activity.
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PMID:Characterization of the calmodulin-binding and of the catalytic domains of Bordetella pertussis adenylate cyclase. 253 1

The effects of cyclic AMP on the rise in cytosolic free calcium concentration, [Ca2+]i, after stimulation with 15 mM K+ in rat brain synaptosomes were investigated. The fluorescent chelating agent Quin-2 was employed to monitor alterations of K+-evoked [Ca2+]i. Under normoxic conditions, clonidine (1, 10 microM), an alpha 2-adrenoceptor agonist, decreased the 15 mM K+-evoked [Ca2+]i. Although yohimbine (1, 10 microM), an alpha 2-adrenoceptor antagonist, had little or no effect on K+-evoked [Ca2+]i, the inhibitory effects of clonidine were blocked by yohimbine. 8-Bromo cyclic AMP, a cyclic AMP analogue, (50-500 microM), increased K+-evoked [Ca2+]i in a dose-dependent manner. The addition of cyclic AMP analogues subsequent to clonidine treatment reversed the clonidine-induced suppression of K+-evoked [Ca2+]i. On the other hand, under hypoxic conditions, K+-evoked [Ca2+]i was reduced by about 50-60%. 8-Bromo cyclic AMP and the adenylate cyclase activators, yohimbine (1-10 microM) and isoproterenol, a beta-adrenoceptor agonist, (0.1-10 microM), transiently reversed the reduction of the K+-evoked [Ca2+]i caused by hypoxia. These results indicate that the activation of alpha 2-adrenoceptor produces a rapid, sustained decrease in [Ca2+]i which may be due to a decrease in the levels of intracellular cyclic AMP. In addition, the increase in cellular levels of cyclic AMP reversed the reduction of the Ca2+ response to high K+ stimulation caused by hypoxia. If this is so, there is the possibility that increased cyclic AMP might improve the hypoxic damage.
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PMID:Relationship of calcium and adenylate cyclase messenger systems in rat brain synaptosomes. 255 13

We show the involvement of chloride transport on excitatory amino acids-induced accumulation of cyclic AMP in brain slices. The stimulation of cyclic AMP formation induced by excitatory amino acids in guinea pig hippocampal slices was absolutely dependent on the presence of Cl- in the incubation medium. The apparent half-maximal concentration of chloride was about 30 to 40 mM with the maximum response at more than 60 mM. As regards to the anion selectivity for the stimulation by excitatory amino acids, Br- was fully effective as Cl-, whereas F- and SO42- were ineffective. DL-(+/-)-2-Amino-4-phosphonobutyric acid, an antagonist of excitatory amino acid receptors, reduced significantly the response to excitatory amino acids. In the Cl- -free medium, the stimulatory effects of 50 microM veratridine, 10 microM forskolin and 100 microM histamine were reduced markedly but still significantly observed. The anion exchange blockers at the concentrations of more than 1 mM reduced significantly the cyclic AMP formation induced by an excitatory amino acid in a dose-dependent manner. Furosemide at the concentration of 3 mM negated the Cl- -dependent responses to forskolin and histamine without affecting the Cl- -independent ones. Furosemide did not inhibit the adenylate cyclase activity of hippocampal synaptic membrane fractions.
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PMID:Mechanism of excitatory amino acid-induced accumulation of cyclic AMP in hippocampal slices: role of extracellular chloride. 283 39

The hormonal regulation of Na+-dependent phosphate transport was studied in opossum kidney (OK) cells. PTH caused time- and concentration-dependent decreases in Na+-dependent phosphate transport, with 10 pM PTH-(1-34) producing a 19% decline in phosphate transport. The EC50 for PTH inhibition of phosphate transport was 50 pM. Kinetic analyses of phosphate transport indicated that PTH decreased the maximum velocity without affecting the Km for phosphate. PTH increased cAMP formation with an EC50 of 10 nM. 8-Bromo-cAMP and (Bu)2cAMP also inhibited phosphate transport. Forskolin increased cAMP formation and decreased phosphate transport, whereas the cyclase-inactive forskolin analog 1,9-dideoxyforskolin also inhibited phosphate transport. The PTH analog [8,18-norleucine,34-tyrosinamide]PTH-(3-34) reduced phosphate transport at concentrations from 10 nM to 30 microM, but did not increase cAMP formation at concentrations up to 10 microM. The adenylate cyclase inhibitor 2',5'-dideoxyadenosine produced concentration-dependent decreases in PTH-stimulated cAMP formation, but did not influence PTH inhibition of Na+-dependent phosphate transport. Vasoactive intestinal polypeptide and prostaglandin E1 increased cAMP formation in OK cells, but were weak inhibitors of phosphate transport. This study suggests that cAMP may not be the only transmembrane signaling mechanism involved in the regulation of Na+-dependent phosphate transport by PTH-(1-34) in OK cells.
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PMID:Regulation of sodium-dependent phosphate transport by parathyroid hormone in opossum kidney cells: adenosine 3',5'-monophosphate-dependent and -independent mechanisms. 283 79


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