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)

Cytochemical techniques have been employed to study the localization of adenylate cyclase and (Ca2+ + Mg2+)-stimulated ATPase activities in platelets after fixation. Biochemical analysis of adenylate cyclase demonstrated a 70% reduction in activity in homogenates from fixed cells, but the residual activity could be stimulated 10--20 times by prostaglandin E1 (1 micrometer) under the same incubation conditions as employed in the cytochemical studies (e.g. media containing 2 mM lead nitrate and 10 mM NaF). Adenylate cyclase activity employing 5'-adenylyl-imiodiphosphate (AMP-P(NH)P) as substrate was found to be associated with the dense tubular system (smooth endoplasmic reticulum) in intact fixed platelets, and was apparent only when the cells were incubated with prostaglandin E1. Less activity was found along the membranes of the surface connected open canalicular system and occasionally at the outer cell surface. Enzymatic activity was blocked by the adenylate cyclase inhibitor 9-(tetrahydro-2-furyl) adenine and was not due to AMP-P(NH)P phosphohydrolase activity. The low adenylate cyclase activity in the surface membranes may be due to enzyme inactivation as a result of fixation, since a surface membrane fraction obtained by the glycerol lysis technique from unfixed cells had an adenylate cyclase specific activity equivalent to that in the microsomal membrane fraction. (Ca2+ + Mg2+)-stimulated ATPase activity was found associated with the membranes of the surface connected open canalicular system in unfixed cells. After brief fixation (5--15 min) with glutaradehyde, strong (Ca2+ + Mg2+)ATPase activity became apparent in the dense tubular system. Longer periods of fixation inactivated enzymatic activity. Addition of Ca2+ (1.0 mM) to incubation medium with low Mg2+ (0.2 mM), or increasing Mg2+ to 4.0 mM, in both cases strongly stimulated enzyme activity. The ATPase activity in the platelet membranes was not inhibited by ouabain. It is suggested that the Ca2+-stimulated ATPase and adenylate cyclase activities in the dense tubules may possibly be involved in regulation of intracellular Ca2+ transport.
Biochim Biophys Acta 1978 Sep 06
PMID:Cytochemical localization of adenylate cyclase and of calcium ion, magnesium ion-activated ATPases in the dense tubular system of human blood platelets. 15 Aug 66

Basal adenylate cyclase activity was increased in red cell ghosts from both patients with Duchenne muscular dystrophy and their mothers when the activities were compared to proper age-matched controls. The activity of ATPase measured in the presence of Na+, K+, and Mg2+ was not found to be different in erythrocyte ghosts from Duchenne dystrophic patients, age-matched controls, or the mothers of Duchenne patients, and ouabain inhibited ATPase in ghosts to the same extent in all membrane preparations.
Clin Chim Acta 1979 Sep 03
PMID:Adenylate cyclase and ATPase activities in red cell membranes of patients and genetic carriers of Duchenne muscular dystrophy. 15 46

Cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were slightly increased in preleukemic AKR mouse thymus cells, compared with nonleukemic thymus cells, but were markedly reduced in leukemic cells. Adenylate cyclase activity rose during the preleukemic and leukemic phases of leukemogenesis. Although the drop of epinephrine-induced stimulation of thymus adenylate cyclase in the preleukemic phase was probably age related, there was an additional decrease of adenylate cyclase activation by epinephrine in leukemic cells. Cyclic AMP phosphodiesterase activity was slightly higher in preleukemic cells and more than fourfold AKR thymus. These observations suggest that cyclic AMP phosphodiesterase is largely responsible for the low levels of cyclic AMP in leukemic cells. Significant changes in cyclic AMP metabolism are already detectable before neoplastic cells may be found in the thymus.
Cancer Res 1975 Sep
PMID:Changes in lymphoid cyclic adenosine 3':5'-monophosphate metabolism during murine leukemogenesis. 16 59

Lithium (Li+) chloride, 2 to 3 mEq. per kilogram of body weight, was administered intraperitoneally to normal Wistar rats daily for 4 to 66 days. This resulted in a marked reduction in urine osmolality (Uosm.) and increase in the excretion of water, Na+, K+, uric acid, and phosphate. The excretion of uric acid and potassium was a direct function of UNaV. The magnitude of depression in urine osmolality was significantly related to the rate of excretion of lithium in the urine, suggesting that the change in water reabsorption is dependent on the presence of the ion in the luminal side of the tubule. During 2 per cent saline diuresis, Li+-treated rats achieved less fractional free water reabsorption (TcH2O/GFR times 100) at any level of fractional osmolar clearance (Cosm./GFR times 100) than normal rats. On the other hand, during 0.225 per cent saline diuresis, fractional free water clearance (CH2O/GFR times 100) was normal over a wide range of fractional urine flow (V/GFR times 100), indicating intact function of the ascending limb of the loop of Henle. The intravenous infusion of vasopressin (VP) or dibutyryl cyclic-adenosine monophosphate (dcAMP) to Li+-treated rats resulted in a modest rise in Uosm. and a reduction in V/GFR times 100 and CH2O/GFR times 100. Although the response to VP appeared earlier than that to dibutyryl cyclic-AMP, the magnitude of the changes in Uosm., V/GFR times 100, and CH2O/GFR times 100 was eventually the same with both substances. Comparison between normal and Li+-treated rats revealed that the response to both VP and dibutyryl cyclic-AMP was blunted, albeit to a greater extent in the former. Inhibition by Li+ of adenylate cyclase will only partially explain the present data. Impairment in the release of endogenous VP or a block distal to the formation of cyclic-AMP must have played a role. In view of a normal diluting capacity and the increase in the excretion of phosphate and uric acid, it is suggested that Li+, when administered chronically in the present doses, inhibits proximal tubular reabsorption.
J Lab Clin Med 1975 Sep
PMID:Renal effects of lithium administration in rats: alterations in water and electrolyte metabolism and the response to vasopressin and cyclic-adenosine monophosphate during prolonged administration. 16 79

Parathyroid hormone, calcitonin, and prostaglandin E2 activate the adenylate cyclase-cyclic AMP system in fetal-rat calvaria. These agents presumably interact with the tissue at separate receptor sites. When calvaria were preincubated with trypsin, 500 mug/ml for 45 min, the subsequent increase in 3',5'-AMP in response to parathyroid hormone was markedly diminished, whereas the response to calcitonin and prostaglandin E2 were not altered significantly. The effect was attributable to an action of the enzyme on the tissue and not to hydrolysis of the hormone. Similarily, preincubation of calvaria with trypsin prior to homogenization and preparation of a crude plasma membrane fraction decreased PTH-sensitive adenylate-cyclase activity by 58% but did not alter the degree of stimulation of the enzyme in response to calcitonin, prostaglandin E2, or sodium fluoride. These studies support the hypothesis that the actions of parathyroid hormone and calcitonin on bone are mediated through distinct receptor sites, and the receptors for parathyroid hormone can be altered selectively with trypsin.
Metabolism 1975 Sep
PMID:Selective proteolysis of the receptor for parathyroid hormone in skeletal tissue. 16 56

Adenylate cyclase (EC 4.6.1.1) and several carbohydrate permeases are inhibited by D-glucose and other substrates of the phosphoenolpyruvate:sugar phosphotransferase system. These activities are coordinately altered by sugar substrates of the phosphotransferase system in a variety of bacterial strains which contain differing cellular levels of the protein components of the phosphotransferase system: Enzyme I, a small heat-stable protein, and Enzyme II. It is suggested that the activities of adenylate cyclase and the permease proteins are subject to allosteric regulation and that the allosteric effector is a regulatory protein which can be phosphorylated by the phosphotransferase system.
J Biol Chem 1975 Sep 10
PMID:Coordinate regulation of adenylate cyclase and carbohydrate permeases by the phosphoenolpyruvate:sugar phosphotransferase system in Salmonella typhimurium. 16 65

The failure of certain adrenal tumors to respond to ACTH was investigated in vivo be administration of corticotropin-(1-24)-tetracosapeptide (ACTH1-24) and dexamethasone and in vitro by studying the binding properties of ACTH1-24 and prostaglandin E1 (PGE1) and their effect on adenylate cyclase activity of the tumors' crude membranes; in addition, in five cases the stimulation of cortisol production in isolated adrenal cells by both hormones and dibuttyryl cyclic adenosine 3',5'-monophosphate (cAMP) was also studied. The results obtained in 13 hormone-producing tumors of the human adrenal cortex, i.e. 10 carcinomas and 3 adenomas, were compared with those found in normal human adrenal glands. According to the adenylate cyclase responses to ACTH1-24 and PGE1, the tumors fall into different categories. In the first group are six rumors in which the adenylate cyclase was stimulated by both ACTH1-24 and PGE; in addition specific binding could be demonstrated for the two hormones in all six. The binding affinity for 125I-ACTH1-24 was found to be about 10 times higher than that for 125I-ACTH11-24. In the one tumor in which the experiment was performed, bound 125I-ACTH1-24 was displaced by ACTH1-10. These results are similar to the ones found in normal human adrenal preparations. For two rumors of the group in which ACTH did not increase steroidogenesis in vivo, the biochemical abnormality might be located beyond cAMP formation. A second group encompasses six tumors in which the steroidogenesis in vivo and the adenylate cyclase activity were insensitive to ACTH1-24 but in which the enzyme was stimulated by PGE1 and NaF. However, these preparations bound 125I-ACTH1-24 and 125I-ACTH11-24, the binding affinity being similar for both peptides but 10 times lower than the one found in normal adrenal cortex for 125I-ACTH1-24. In the only case of this group where it was tested, ACTH1-10 did not displace bound 125I-ACTH1-24. This result strongly suggests the possibility of a modification or a loss of the receptor site that binds the N-terminal sequency (1-10) of ACTH, the biologically active part of the molecule. In the last tumor, both PGE1 and ACTH were unable to stimulate adenylate cyclase activity and steroid production in a preparation of isolated adrenal cells, although steroidogenesis was stimulated by dibutyryl though steroidogenesis was stimulated by dibutyryl cAMP. No specific binding for PGE1 could be demonstrated. However, 125I-ACTH1-24 and 125I-ACTH11-24 were found to be bound to the tumor with the same affinity.
J Clin Invest 1975 Sep
PMID:ACTH and prostaglandin receptors in human adrenocortical tumors. Apparent modification of a specific component of the ACTH-binding site. 16 92

Adenylate cyclase was assayed in pellets prepared by centrifuging for 10 min at 600 x g homogenates of ovaries of immature rats treated with PMS and hCG. Activity was detected in the absence of any stimulatory agents and increased markedly in the presence of fluoride. Dose-dependent activity occurred in vitro in response to LH ranging from 0.2 to 10 mug/ml of incubate but not at higher concentrations. Marked changes in adenylate cyclase activities were observed with preparations from ovaries excised at various times after gonadotropin treatment. These changes, measured as the response to both fluoride and LH were observed to occur in four main stages. An initial decrease occurred 1/2 to 1 day after administration of hCG. Activity then increased and remained significantly elevated from day 3 to 7. A second but more dramatic rise was observed on day 8 and this enhanced level of activity remained elevated until day 13. A decreased level of activity occurred on day 15. Unstimulated activity remained low for the 16 day period studied although significant rises were observed on day 3 and days 8 to 15 after the administration of hCG. We have suggested that these changes in the adenylate cyclase activity modulate the level of cyclic AMP in the luteal cells and thereby induce changes in the activity of enzymes involved in progestin biosynthesis.
Endocrinology 1975 Sep
PMID:The effects of exogenous gonadotropins on ovarian adenylate cyclase activity. 17 66

The radioactive adenosine 3',5'-monophosphate (cyclic AMP) level derived from 8-14C adenine in intact rabbit platelets decreased in the presence of mitochondrial inhibitor (potassium cyanide) or uncoupler (sodium azide), and markedly increased by the addition of NaF, monoiodoacetic acid (MIA), or 2-deoxy-D-glucose. The stimulative effect of the glycolytic inhibitors was distinctly enhanced by the simultaneous addition of sodium succinate. MIA did neither directly stimulate the adenyl cyclase activity nor inhibit the phosphodiesterase activity. These results suggest that cyclic AMP synthesis in platelets is closely linked to mitochondrial oxidative phosphorylation.
Thromb Diath Haemorrh 1975 Sep 30
PMID:Dependence of platelet adenyl cyclase system on oxidative phosphorylation. 17 98

A mildly obese 15-year-old boy had short stature with rounded facies and short, stubby hands and toes. He had the fully expressed syndrome of pseudohypoparathyroidism but was the only member of his family who had all the somatic characteristics of this disease. The serum parathyroid hormone level was substantially elevated. Urinary excretion of cyclic adenosine monophosphate and phosphate failed to increase following intravenous infusion of parathyroid hormone. However, he did not have hypocalcemia. The present entity is probably a transient form of pseudohypoparathyroidism with partial responsiveness of skeletal adenyl cyclase to parathyroid hormone.
Am J Dis Child 1975 Sep
PMID:Pseudohypoparathyroidism with normal serum calcium level. 17 42


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