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)

Fractions enriched in hCG-binding activity were prepared by differential rate centrifugation of superovulated rat ovarian homogenates and were applied to continuous sucrose density gradients (20-55%). After centrifugation at 63,000 x gav for 3.5 h, fractions of each gradient were collected and assayed for a range of marker enzyme activities characteristic of surface membranes and subcellular organelles. Mitochondria, lysosomes, and rough and smooth endoplasmic reticulum membranes accumulated in the gradient between 38-41% sucrose (1.165-1.180 g/cm3). Nuclei passed through the gradient. However, the various surface membrane markers concentrated in two distinct regions of the gradient. Alkaline phosphatase, phosphodiesterase, (Na+ + K+)ATPase I, and hCG-binding activity concentrated at 29-32% sucrose (1.120-1.135 g/cm3), whereas 5'-nucleotidase, Mg2+-dependent ATPase, and adenylate cyclase activities (and minor peaks of hCG-binding and phosphodiesterase activities) were enriched at 36-38% sucrose (1.16-1.17 g/cm3). A second ATPase, [(Na+ + K+)ATPase II], was also observed in this region of the gradient, which could be distinguished from (Na+ + K+)ATPase I of the light membrane fraction by its sensitivity to the Ca2+-chelating agent, ethylene glycol bis-(aminoethyl)tetraacetic acid (EGTA). The kinetics of binding of radioiodinated hCG to the gonadotropin receptors of the light and heavy membrane fractions were very similar. It is suggested that fractionation of superovulated rat ovaries yields two distinct populations of surface membrane material which have distinct densities and marker enzyme profiles. Furthermore, in contrast to the heavy membrane fraction, light membranes seem to possess considerable amounts of hCG receptor activity but very little adenylate cyclase.
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PMID:Interactions of gonadotropins with corpus luteum membranes. II. The identification of two distinct surface membrane fractions from superovulated rat ovaries. 21 57

Using tunicamycin, we have investigated the role of glycoproteins in membrane transport. Tunicamycin is a glucosamine-containing antibiotic that specifically inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues of glycoproteins. Inhibition of protein glycosylation in chick embryo fibroblasts by tunicamycin or other inhibitors of glycosylation resulted in defective transport of glucose, uridine, and amino acid analogs (alpha-aminoisobutyrate and cycloleucine). The defect in glucose transport is accompanied by decreased glucose metabolism, as determined by rates of CO2 and lactate production. In contrast, tunicamycin treatment did not affect other membrane-associated processes, such as secretion of fibronectin and procollagen, uptake of glucose by passive diffusion, Na+/K+ ATPase and adenylate cyclase activities, or stimulation of adenylate cyclase by prostaglandin and cholera toxin. Two glucose/glycosylation-regulated membrane proteins with apparent subunit molecular weights of 95,000 and 75,000 were induced by tunicamycin treatment. Our results indicate that glycoprotein glycosylation is required for membrane transport.
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PMID:Evidence for role of glycoprotein carbohydrates in membrane transport: specific inhibition by tunicamycin. 21 20

Plasma membranes were obtained from a homogeneous population of rabbit red blood cells at different maturation periods. Minor modifications in membrane proteins and membrane phospholipids and significant decreases in membrane glycoproteins and total lipids were observed with the age of the cell. The ouabain inhibited (Na+K+)-ATPase and the adenylate cyclase decreased with maturation but acetylcholinesterase and 5'-nucleotidase remained almost unchanged. The apparent activation energy of the ATPase increased with maturation. The results indicate that structural and functional modifications of the plasma membrane occur concomitantly with the ageing processes of the red cell.
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PMID:Studies of the plasma membrane during maturation of the mammalian erythrocyte. 21 11

Cell surface membrane fragments were isolated and purified by successive rate zonal and isopycnic centrifugation of calcium oxalate-loaded pigeon heart microsomes in sucrose density gradients. The most highly purified cell membrane fraction sediments at a buoyant density of 1.105 g/ml. Some of the membrane pieces are present as open fragments and leaky vesicles, while others form tightly sealed vesicles of both inside-in and inside-out membrane orientation. The pigeon heart cell membrane preparation exhibits high (Na+ + K+ + Mg2+)-ATPase and adenylate cyclase activities. Additional activity of these enzymes is uncovered by sodium dodecyl sulfate and alamethicin, respectively. Electron microscopic inspection of the cell surface membrane preparation revealed (a) a predominance of thick-walled vesicles with smooth surfaces on negative staining and (b) binding of concanavalin A to the bulk of isolated membrane pieces following their incubation with the lectin.
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PMID:Mass isolation of cell surface membrane fragments from pigeon heart. 22 Oct 21

A mixed membrane preparation obtained from turtle bladder epithelial cells contains (Na+ + K+)-ATPase, adenylate cyclase and protein kinase, which interact with ouabain, norepinephrine and cyclic AMP, respectively. When such a preparation is obtained from bladders which had been preexposed to serosal fluids containing the tritiated form of 4,4'-diisothiocyano-2,2'-disulfonic stilbene, the subsequently isolated membrane proteins are enriched in tritium as well as in the afore-mentioned enzymes, none of which is inhibited. Free-flow electrophoresis separates the mixed membrane preparation into two distinguishable groups: one, construed as apical membranes, is enriched in norepinephrine-sensitive adenylate cyclase and cyclic AMP-sensitive protein kinase; the other, construed as basal-lateral membranes, is enriched in ouabain-sensitive ATPase and 4,4'-diisothiocyano-2,2'-disulfonic stilbene-binding proteins. The physiological counterparts of these enzymatically defined membrane markers are the mucosal sidedness of the transport effects of norepinephrine and cyclic AMP derivatives and the serosal sidedness of the transport effects of ouabain and disulfonic stilbenes in the intact turtle bladder. The discreteness and ion selectivity of each membrane-bound, transport-related element are discussed in relation to the corresponding characteristics of each transport process in vivo; the possibility of regulation of anion transport by adenylate cyclase-protein kinase system is also discussed.
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PMID:Localization and characterization of transport-related elements in the plasma membrane of turtle bladder epithelial cells. 22 43

In studies conducted over the last 10 years, the ATP, ADP, AMP concentrations, the adenylate pool (ATP + ADP + AMP), the "energy charge" and the cAMP levels were determined:(1) in gastric tissues of pylorus-ligated rats, (2) in gastric and duodenal mucosa and muscular layer (musculature) of human subjects qualified as "hypacid", "normacid" and "hyperacid" on the basis of basal (BAO) and maximal acid output (MAO), (3) in ulcer-bearing and non-ulcerous antral, duodenal and jejunal mucosa and muscular layer of patients with peptic ulcer, including chronic (essential) antral, duodenal ulcer and jejunal ulcer following gastric resection of Billroth II-type. Close analysis of the results centres on: (1) the biochemical background of gastric hypersecretion and of ulcerogenesis in pylorus-ligated rats;(2) the extra- and intracellular feedback system operating between the gastric membrane ATPase and adenylate cyclase systems, under normal and abnormal conditions of the effector organ; (3) questions related to the regulatory mechanisms of functional activity of the effector organ under drug effect; (4) the energy structure of the mucosa and muscular layer of corpus ventriculi, antrum and duodenum in patients considered "hypacid", "normacid" and "hyperacid" on the grounds of the BAO and MAO values; (5) the interrelationships between human gastric H+--K+-dependent ATPase system of gastric corpus mucosa; (6) pharmacological regulation of the ATP--ADcer-free mucosa and musculature of patients with antral, duodenal and jejunal ulcers.
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PMID:The energy systems of gastric tissues, their neural, hormonal and pharmacological regulations in order to gastric H+ secretion and ulcerogenesis. (A review of animal experiments and clinical biochemical studies). 23 Jun 86

The rectal gland of the spiny dogfish, Squalus acanthias, provides an easily studied model of active chloride transport powered indirectly by Na-K-ATPase. Co-transport of sodium with chloride can be demonstrated in membrane vesicles isolated from basolateral membranes of the gland. Chloride secretion is under the hormonal control of vasoactive intestinal peptide, and possibly other agents, via adenyl cyclase and cyclic AMP. A similar mechanism is probably responsible for the active transport of chloride across other biological membranes.
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PMID:The shark rectal gland: a model for the active transport of chloride. 23 64

Various mechanisms have been proposed for beta-adrenergically mediated relaxation of smooth muscle. All theories suggest the involvement of cyclic AMP as a second messenger: beta-agonists stimulate adenylate cyclase which converts ATP to cyclic AMP and protein kinase, activated by cyclic AMP, is then thought to catalyse a protein phosphorylation that leads to a reduction in free Ca2+, thus effecting relaxation. How this last step is accomplished is much debated, but the following possibilities are currently considered as the mechanisms responsible for cyclic AMP-induced reduction of cytoplasmic Ca2+: activation of a Ca2+-ATPase in the plasma and/or sarcoplasmic reticulum membranes which lowers cytoplasmic [Ca2+] in a direct manner or stimulation of (Na+-K+)ATPase in the cell membrane which may indirectly effect Ca2+ extrusion. Among the hypotheses suggested, those of Ca2+ sequestration by the sarcoplasmic reticulum and of Ca2+ extrusion across the cell membrane are consistent with each other if it is assumed that both processes are effected by a cyclic AMP-sensitive Ca2+-ATPase. However, quite a different mechanism is implied by involving the Na+-K+ pump and Na+-Ca2+ exchange carrier. In this report, we present evidence that suggests intracellular Ca2+ sequestration is the mechanism involved.
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PMID:Role of intracellular Ca2+ sequestration in beta-adrenergic relaxation of a smooth muscle. 23 30

The role and pharmacological regulation of the ATP-adenylate-cyclase--cAMP system were studied in the mucosa of the gastric fundus, and in the forestomach, of pylorus-ligated rats to elucidate the development of gastric hypersecretion and ulceration. (1) cAMP content of the tissue of the fundus mucosa and of the forestomach decreased before the significant increase of gastric H+ output and ulcer development; (2) the gastric H+ outputs depended on the breakdown of ATP in the fundus mucosa; (3) the gastric H+ secretion was inhibited in a dose-dependent way by theophylline, epinephrine and cimetidine; (4) the inhibition of gastric H+ secretion by epinephrine , theophylline or epinephrine plus theophylline associated with a significant increase in the mucosal cAMP of the gastric fundus (5) the significant increase in gastric H+ secretion due to histamine associated with a significant decrease in fundic mucosal cAMP; (6) the gastric H+ secretion could be inhibited dose-dependently by ADP, AMP, cyclic 2', 3'-AMP and cAMP; (7) the inhibition of gastric H+ secretion by cimetidine developed without and with histamine application in pylorus-ligated rats; (8) the histamine on gastric H+ secretion could not be stimulated further with theophylline (9) no significant correlation was found between the mucosal cAMP level and the gastric H+ secretion and/or between the decrease of mucosal cAMP content and gastric H+ secretion. It has been concluded that in pylorus-ligated rats (1) the gastric H+ secretion is an ATP-dependent process; (2) the cAMP system has an inhibitory effect as regards the development of gastric hypersecretion and of ulceration; (3) histamine and cimetidine show no close correlation with the cAMP system; (4) an extracellular and intracellular feed-back mechanism system exists between th ATP-membrane-bound ATPase-ADP and the ATP--adenylate cyclase--cAMP systems in the background of the development of gastric hypersecretion and ulceration.
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PMID:The role of the ATP--adenylate cyclase--cAMP system and its pharmacological regulation in the development of gastric hypersecretion and ulceration. 23 1

The inhibitory effects of atropine, epinephrine, cyclic 3', 5'-AMP (cAMP), the prostaglandins E1 (PGE1) and E2 (PGE2) pentagastrin, histamine and ouabain have been studied on the activity of Na+--K+-dependent ATPase obtained from human gastric fundic mucosa. This study compares the sensitivity of the enzyme to a variety of drugs, applying the law of one receptor and more drugs. It was found that (1) the doses of drugs necessary to produce 50% inhibition to Na+--K+-dependent ATPase activity (affinity, pD2 value) significantly differ from each other C (atropine, 9.50; epinephrine, 8.60; cAMP: 11.30; PGE1, 9.30; PGE2, 9.45; pentagastrin, 9.45; histamine, 9.70 and ouabain, 9.50); (2) the intrinsic activities of drugs to Na+--K+-dependent, ATPase in comparison with ouabain (alpha=1.00) differ: atropine, PGE1, PGE2 and histamine, 1.00; pentagastrin, 0.87; cAMP, 0.48 and epinephrine, 0.41; (3) the inhibitory effects of different drugs, on Na+--K+-dependent ATPase system, depend on the magnitude of enzyme activity from human gastric fundic mucosa. It has been concluded that (1) the sensitivity of these drugs to the Na+--K+-dependent ATPase system and to the adenylate cyclase system, both obtained from human gastric mucosa, significantly differs from each other; (2) the main effect of pentagastrin and histamine on human gastric secretory function differs from the function of Na+--K+-dependent ATPase system; (3) the role of Na+--K+-dependent ATPase system and of adenylate cyclase can be separated pharmacologically from the point of view of human gastric H+ secretion.
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PMID:A comparative molecular--pharmacological study of drugs inhibiting Na+--K+-dependent ATPase separated from human gastric fundic mucosa. (One receptor system and more drugs). 23 2


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