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 105 000 X g gupernatant fractions from homogenates of various rat tissues catalyzed the formation of both cyclic GMP and cyclic AMP from GTP and ATP, respectively. Generally cyclic AMP formation with crude or purified preparations of soluble guanylate cyclase was only observed when enzyme activity was increased with sodium azide, sodium nitroprusside, N-methyl-N'-nitro-N-nitrosoguanidine, sodium nitrite, nitric oxide gas, hydroxyl radical and sodium arachidonate. Sodium fluoride did not alter the formation of either cyclic nucleotide. After chromatography of supernatant preparations on Sephadex G-200 columns or polyacrylamide gel electrophoresis, the formation of cyclic AMP and cyclic GMP was catalyzed by similar fractions. These studies indicate that the properties of guanylate cyclase are altered with activation. Since the synthesis of cyclic AMP and cyclic GMP reported in this study appears to be catalyzed by the same protein, one of the properties of activated guanylate cyclase is its ability to catalyze the formation of cyclic AMP from ATP. The properties of this newly described pathway for cyclic AMP formation are quite different from those previously described for adenylate cyclase preparations. The physiological significance of this pathway for cyclic AMP formation is not known. However, these studies suggest that the effects of some agents and processes to increase cyclic AMP accumulation in tissue could result from the activation of either adenylate cyclase or guanylate cyclase.
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PMID:Synthesis of adenosine 3',5'-monophosphate by guanylate cyclase, a new pathway for its formation. 3 26

Homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h) and rat liver were studied with regard to their relative basal activties of adenylate cyclase and to the comparative responsiveness of this enzyme to glucagon, sodium fluoride, epinephrine, prostaglandin E1, and insulin. The basal adenylate cyclase activities of the hepatoma fractions were found to be similar to those of liver at an adenosine 5'triphosphate concentration of 3.2 mM; if the substrate affinity (Km adenosine 5'-triphosphate) of the tumor enzyme is comparable to that of liver, these findings suggest that the reduced basal cyclic adenosine 3':5'-monophosphate levels found to occur in hepatoma 5123tc (h) probably are not due to a decreased basal rate of formation of this cyclic nucleotide. Glucagon (5.6 muM) significantly stimulated adenylate cyclase in both fractions of hepatoma and livers; however, the responsiveness of the tumor enzyme to this hormone was substantially lower than the responsiveness of liver for both homogenate and plasma membrane preparations; i.e., activities were enhanced 18-fold (relative to the basal activity)for liver homogenate compared with only a 6-fold increase for tumor. With the plasma membrane preparations, glucagon increased the activities 5- and 3.5-fold in liver and hepatoma, respectively. Sodium fluoride (10mM), in contrast to glucagon, increased the adenylate cyclase activity to approximately the same extent (about 10-fold) in the liver and hepatoma preparations. Epinephrine (100 muM) enhanced the liver and hepatoma homogenate activites 3- to 4-fold and the hepatoma plasma membrane activities 2-fold; however, the liver plasma membrane activites were not increased. Prostaglandin E1 (56.6 MUM) significantly increased adenylate cyclase activites of liver and hepatoma homogenates (i.e., 1.5- and 3-fold, respectively) but not of the plasma membrane preparations. Insulin (0.7 muM) did not significantly alter adenylate cyclase activities in any of the preparations.
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PMID:Comparative adenylate cyclase activities in homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h). 16 85

The age-dependent relationships between glucagon-induced alterations in myocardial mechanics and adenylate cyclase activity in fetal and newborn lambs and adult sheep were evaluated. Glucagon substantially augmented the force of contraction of ventricular myocardium isolated from the adult but not from the fetus or newborn. Similarly, substantial increases in the spontaneous frequency of contraction and tension were observed in adult atrial strips, but not in the fetus or newborn. Comparable activities of phosphodiesterase were observed in extracts from fetal and adult myocardium and were unaltered by the addition of glucagon. Adenylate cyclase activity in adult myocardial homogenate and particulate fractions was comparable to that of fetal tissue. Glucagon stimulation of the particulate fraction produced no change in fetal adenylate cyclase activity whereas a 43% increase in activity was observed in preparations from adult tissue. Sodium fluoride and epinephrine augmented adenylate cyclase activity in both fetal and adult myocardium. Thus, glucagon produced age-dependent, parallel changes in heart rate, active tension development, and particulate fraction adenylate cyclase activity, suggesting that these chronotropic and inotropic responses are indeed mediated by adenylate cyclase and that lack of response in the fetus reflects the absence of mature glucagon receptor sites.
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PMID:Age-dependent mechanical and biochemical responses to glucagon. 18 Aug 16

The phosphaturic effect of parathyroid hormone (PTH), cyclic adenosine monophosphate (cAMP), acetazolamide (Az), and HCO3 loading was studied in normal, thyroparathyroidectomized (TPTX), and Li-treated dogs. PTH administration to normal animals markedly increased fractional excretion (F) of PO4 but had a blunted effect on FPO4 in the Li-treated animals. Cyclic AMP likewise markedly increased FPO4 in the normal animals but had a markedly blunted effect in the Li-treated animals. Az led to a significant increase in FNa, FHCO3, and FPO4 in the normal animals. In the Li-treated dogs, Az induced a significant natriuresis and bicarbonaturia but failed to increase phosphaturia. HCO3 loading in normal dogs caused a significant phosphaturia while having little effect on FPO4 in Li-treated dogs. HCO3 loading to TPTX dogs was associated with a lower FPO4 as compared to normal HCO3-loaded animals. These data suggest that Li administration not only blocks the adenyl cyclase-cAMP system in the renal cortex, but it may also interfere with a step distal to the formation of cAMP, since the phosphaturic effect of both PTH and cAMP was markedly diminished in Li-treated animals.
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PMID:Lithium administration and phosphate excretion. 18 11

The characteristics of the cholera toxin-stimulated adenylate cyclase of toad (Bufus marinus) and rat erythrocyte plasma membranes have been examined, with special emphasis on the response to purine nucleotides, fluoride, magnesium and catecholamine hormones. Toad erythrocytes briefly exposed to low concentrations of cholera toxin (40,000 to 60,000 molecules per cell) and incubated 2 to 4 hr at 30 degrees C exhibit dramatic alterations in the kinetic and regulatory properties of adenylate cyclase. The approximate Km for ATP, Mg++ increases from about 1.8 to 3.4 mMin the toxin-stimulated enzyme. The stimulation by cholera toxin increases with increasing ATP, Mg++ concentrations, from 20 percent at low levels (0.2 mM) to 500 percent at high concentrations (greater than 3 mM). Addition of GTP, Mg++ (0.2 mM) restores normal kinetic properties to the toxin-modified enzyme, such that stimulation is most simply explained by an elevation of Vmax. GTP enhances the toxin-treated enzyme activity two- to fourfold at low ATP concentrations, but this effect disappears at high levels of the substrate. At 0.6 mM ATP and 5 mM MgC12 the apparent K alpha for GTP, Mg++ is 5 to 10 muM. The control(unstimulated) enzyme demonstrates a very small response to the guanyl nucleotide, 5'-ITP also stimulates the toxin-treated enzyme but cGMP, guanine, and the pyrimidine nucleotides have no effect. Cholera toxin also alters the activation of adenylate cyclase by free Mg++, decreasing the apparent K alpha from about 25 to 5 mM. (minus)-Epinephrine sensitizes the toad erythrocyte adenylate cyclase to GTP and also decreases the apparent K alpha for free metal. Sodium fluoride, which causes a 70- to 100-fold activation of enzyme activity, has little effect on sensitivity to GTP, and does not change the apparent K alpha for Mg++; moreover,it prevents modulation of these parameters by cholera toxin. Conversely, cholera toxin severely inhibits NaF activation, and in the presence of fluoride ion the usual three to fivefold stimulation by toxin becomes a 30 to 60 percent inhibition of activity. The toxin-stimulated enzyme can be further activated by catecholamines; in the presence of GTP the (minus)-epinephrine stimulation is enhanced by two- to threefold. The increased catecholamine stimulation of toad erythrocyte adenylate cyclase induced by cholera toxin is explained primarily by an increase in the maximal extent of activation by the hormones. Rat erythrocyte adenylate cyclase is also modified by cholera toxin. In the mammalian system the apparent affinity for the hormone appears to be increased. Cholera toxin thus induces profound and nearly permanent changes in adenylate cyclase by a unique process which mimics the stimulation by hormones in important ways, and which also accentuates the normal hormonal response. The relevance of these findings to the mechanism of action of cholera toxin is considered.
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PMID:Mechanism of action of Vibrio cholerae enterotoxin. Effects on adenylate cyclase of toad and rat erythrocyte plasma membranes. 80 47

Prolonged hypoxia causes pulmonary hypertension but no change in systemic vasomotor tone. In an effort to define the mechanisms involved, we determined the effects of 3 and 7 days of hypoxia on adenylate cyclase activity and beta-adrenergic receptor binding characteristics in pulmonary and systemic arteries in an adult rat model of hypoxic pulmonary vasoconstriction produced by hypobaria. Basal and stimulated adenylate cyclase activity were measured in crude membrane preparations by radioimmunoassay for cyclic AMP. Basal enzyme activity in pulmonary arteries did not change with hypoxia, whereas in systemic arteries it increased 3.5- and 5.3-fold following 3 and 7 days of hypoxia, respectively. GTP-stimulated activity in pulmonary arteries also did not change, but in systemic arteries it increased 7.1- and 5.5-fold. Isoproterenol-stimulated activity in pulmonary arteries was decreased to 49% of control-stimulated activity following 3 days but was similar to control-stimulated activity after 7 days of hypoxia; in systemic arteries it increased 5.6- and 4.6-fold. Sodium fluoride-stimulated activity in pulmonary arteries was unchanged, whereas in systemic arteries it increased 3.8- and 5.3-fold. In contrast, forskolin-stimulated activity, which also was not altered in pulmonary arteries, was increased by only 85% and 71% in systemic arteries. beta-Adrenergic receptors were studied with [125I]iodocyanopindolol. Seven days of hypoxia decreased receptor density by 37% and 57% in the pulmonary and systemic arteries, respectively. Receptor affinity for agonists was not altered. Thus, despite downregulation of beta-adrenergic receptors in both artery types, prolonged hypoxia has no sustained effect on adenylate cyclase activity in pulmonary arteries, whereas enzyme activity in systemic arteries is markedly increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of prolonged hypoxia on adenylate cyclase activity and beta-adrenergic receptors in pulmonary and systemic arteries of the rat. 216 Aug 69

The effects of adenosine triphosphate (ATP) on short-circuit current (SCC) in rat colonic epithelium are described. ATP caused a large increase in inward-going current and was considerably more potent in this respect than ADP, AMP or adenosine. The response to ATP was sided, there being only minor effects when the nucleotide was added to the apical side of the tissue. The effects of ATP were not modified by the cyclooxygenase inhibitor, indomethacin, eliminating eicosanoid formation as a mechanism. The effects of ATP were potentiated by theophylline and not blocked by alpha, beta-methylene ATP. The data are consistent with the effect being dependent on the activation of adenylate cyclase, but it has not been possible to classify the receptors into P1 or P2 categories. Using inhibitors of NaCl cotransport (piretanide), carbonic anhydrase (acetazolamide), and chloride channels (diphenylamine-2-carboxylate), it was concluded that the SCC response to ATP was due to chloride secretion with, perhaps, a minor contribution from bicarbonate. Flux measurements with 22Na and 36Cl confirmed this view, there being approximate equivalence of chloride secretion with the SCC responses. Additionally, flux measurements revealed an inhibition of electroneutral NaCl absorption in response to ATP. The effects of ATP were antagonized by tetrodotoxin (TTX), greater than 50% inhibition being achieved with 10 nM TTX. This result suggests that ATP does not act directly on receptors in the epithelial cells but rather on neuronal elements in the lamina propria. It will be necessary to re-examine other secretagogues for indirect effects of this kind and to search for the final effector neurotransmitter which evokes secretion.
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PMID:Indirect effects of adenosine triphosphate on chloride secretion in mammalian colon. 241 31

To investigate beta-adrenergic receptor dysfunction in congestive heart failure (CHF), the density of lymphocyte beta receptors and adenylate cyclase activity was measured at rest and at peak exercise in 30 patients with CHF and 7 age-matched control subjects. At rest, patients with CHF had reduced beta-receptor density (normals 33 +/- 2; CHF 21 +/- 2 fmol/mg protein; p less than 0.01) and isoproterenol-stimulated adenylate cyclase activity (normals 50 +/- 9; CHF 28 +/- 4 pmol/mg protein/min; p less than 0.05). Sodium fluoride-stimulated adenylate cyclase activity was also reduced (normals 98 +/- 17; CHF 48 +/- 12 pmol/mg protein/min; p less than 0.01). In the patients with CHF, there was no significant correlation between receptor density and peak exercise VO2, ejection fraction or resting plasma catecholamines. In the normal subjects, maximal exercise increased beta-receptor density by 100% (rest 33 +/- 2; exercise 67 +/- 7 fmol/mg protein) and isoproterenol-stimulated adenylate cyclase activity by 66% (rest 50 +/- 9; exercise 83 +/- 18 pmol/mg protein/min (both p less than 0.01]. In contrast, patients with CHF exhibited only a 58% increase in beta-receptor density (rest 20 +/- 3; exercise 32 +/- 6 fmol/mg protein; p less than 0.01) and no significant change in isoproterenol-stimulated adenylate cyclase activity (rest 27 +/- 5; exercise 24 +/- 5 pmol/mg protein/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of lymphocyte beta-adrenergic receptors at rest and during exercise in ambulatory patients with chronic congestive heart failure. 253 14

The effects of intrauterine implantation of 17 beta-estradiol and progesterone on basal and stimulated adenylate cyclase activity in guinea pig myometria were studied in nonpregnant, previously oophorectomized guinea pigs receiving intrauterine implants of either estradiol, progesterone, a combination of the two hormones, or placebo for 7 days. Guanine nucleotides resulted in a significant increase in basal enzymatic activity. The extent of enzymatic stimulation in estradiol-treated animals was significantly higher than that observed in either controls, animals receiving progesterone, or a combination of estradiol and progesterone. Sodium fluoride stimulation occurred in all treatment groups to a similar degree. However, guanine nucleotides resulted in a significant decrease in percent stimulation of maximal sodium fluoride-stimulated enzymatic activity. Finally, beta-adrenergic receptor-mediated enzymatic activity, as assayed by isoproterenol stimulation, was higher in those animals that received estradiol implants than in controls or the other two hormonally treated groups. Intrauterine administration of these sex steroid hormones, directly or indirectly, modulates myometrial adenylate cyclase activity.
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PMID:Up-regulation of guinea pig myometrial adenylate cyclase activity by intrauterine estradiol and progesterone pellets. 280 22

Cells of the human medulloblastoma clonal line TE671 exhibit polymorphism when grown in vitro in serum-supplemented medium. Under these conditions, cell numbers double every 18 h during log phase growth. These tumorigenic precursors of cerebellar interneurons are not contact-inhibited and approach densities of one million cells per cm2. TE671 cells in proliferative growth express a class of nicotinic acetylcholine receptors that are fully sensitive to functional blockade by the neurotoxin alpha-bungarotoxin (Bgt). TE671 cells grown in medium containing dibutyryl cyclic adenosine monophosphate (dbcAMP) rapidly undergo a distinctive morphological transformation characterized by neurite extension and formation of cell-cell contacts. The rate of cell division and cell saturation densities are diminished coordinately with these treatments. Sodium fluoride and forskolin induce similar changes in cell division and morphology as does dbcAMP, and these effects are potentiated by aluminum and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, respectively. The high-affinity binding of Bgt to TE671 cells also is reduced on exposure to dbcAMP in a time and dose-dependent manner. The results suggest that activation of adenylate cyclase and the concomitant elevation of intracellular cAMP levels may be involved in the morphological transformation of TE671 cells to a mature, neuronal phenotype and in changes in the level of expression of a subtype of human neuronal nicotinic receptors. These studies establish a unique, neural tube-derived model system for investigation of the mechanisms involved in these processes.
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PMID:Morphological and biochemical differentiation of the human medulloblastoma cell line TE671. 285 72


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