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)

1. Renal tubular membranes from rat kidneys were prepared, and adenylate cyclase activity was measured under basal conditions, after stimulation by NaF or salmon calcitonin. Apparent Km value of the enzyme for hormone-linked receptor was close to 1 x 10(-8) M. 2. The system was sensitive to temperature and pH. pH was found to act both on affinity for salmon calcitonin-linked receptor and maximum stimulation, suggesting an effect of pH on hormone-receptor binding and on a subsequent step. 3. KCl was without effect areas whereas CoCl and CaCl2 above 100 muM and MnCl2 above 1 muM inhibited F- -and salmon calcitonin-sensitive adenylate cyclase activities. The Ca2+ inhibition of the response reflected a fall in maximum stimulation and not a loss of affinity of salmon calcitonin-linked receptor for the enzyme. 4. The measurement of salmon calcitonin-sensitive adenylate cyclase activity as a function of ATP concentration showed that the hormone increases the maximum velocity of the adenylate cyclase. GTP, ITP and XTP at 200 muM did not modify basal, salmon calcitonin- and parathyroid hormone-sensitive adenylate cyclase activities. 5. Basal, salmon calcitonin- and F- -sensitive adenylate cyclase activities decreased at Mg2+ concentrations below 10 mM. High concentrations of Mg2+ (100 mM) led to an inhibition of the F- -stimulated enzyme. 6. Salmon calcitonin-linked receptor had a greater affinity for adenylate cyclase than human or porcine calcitonin-linked receptors. There was no additive effect of these three calcitonin peptides whereas parathyroid hormone added to salmon calcitonin increased adenylate cyclase activity, thus showing that both hormones bound to different membrane receptors. Human calcitonin fragments had no effect on adenylate cyclase activity. 7. Salmon calcitonin-stimulated adenylate cyclase activity decreased with the preincubation time. This was due to progressive degradation of the hormone and not to the rate of binding to membrane receptors.
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PMID:Calcitonin-sensitive adenylate cyclase in rat renal tubular membranes. 0 53

The effect of parathyroid hormone and calcitonin on the renal excretion of phosphate, calcium, and cyclic AMP was evaluated in the thyroparathyroidectomized hamster, a mammal apparently reisstant to the phosphaturic effect of parathyroid hormone. Parathyroid hormone did not increase phosphate excretion, although it decreased excretion of calcium and increased urinary excretion of cyclic AMP. This lack of a phosphaturic response to parathyroid hormone was not reversed by administration of 25-OH vitamin D or infusions of calcium or phosphate. Calcitonin, another potentially phosphaturic hormone, also vailed to increase phosphate excretion but markedly elevated urinary excretion of cyclic AMP. In hamsters pretreated with infusion of urinary ammonium chloride, which decreased plasma and urinary pH, both parathyroid hormone and calcitonin increased excretion of phosphate as well as that of cyclic AMP. Acetazolamide had no phosphaturic effect in ammonium chloride-loaded hamsters, and it decreased cyclic AMP and calcium excretion. Alkalinization of urine by acetazolamide did not prevent the phosphaturic effect of parathyroid hormone in ammonium chloride-loaded hamsters, but it blocked the increase in urinary cyclic AMP excretion. Parathyroid hormone and calcitonin both stimulated adenylate cyclase in a cell-free system (600-g pellet) from hamster renal cortex, elevated tissue cyclic AMP levels, and activated protein kinase in tissue slices from hamster renal cortex. In acid medium, the increase in cyclic AMP and activation of protein kinase in response to parathyroid hormone was diminished, but addition of acetazolamide restored responsiveness of both parameters to control values. Acetazolamide, on the other hand, did not influence adenylate cyclase or its response to parathyroid hormone or cyclic AMP phosphodiesterase activity. We conclude that the lack of a phosphaturic effect of parathyroid hormone and calcitonin in the hamster depends on steps in the cellular action of these hormones, steps that are sensitive to pH subsequent to cyclic AMP generation and protein kinase activation. In addition, acetazolamide may potentiate the phosphaturic effect of parathyroid hormone by promoting accumulation of cyclic AMP in tissue. Thus, the hamster is a particularly useful model for studies of syndromes in which there is renal resistance to phosphaturic hormones.
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PMID:Mechanism of resistance to the phosphaturic effect of the parathyroid hormone in the hamster. 1 74

Luminal brush border and contraluminal basal-lateral segments of the plasma membrane from the same kidney cortex were prepared. The brush border membrane preparation was enriched in trehalase and gamma-glutamyltranspeptidase, whereas the basal-lateral membrane preparation was enriched in (Na+ + K+1)-ATPase. However, the specific activity of (Na+ + K+)-ATPase in brush border membranes also increased relative to that in the crude plasma membrane fraction, suggesting that (Na+ + K+)-ATPase may be an intrinsic constituent of the renal brush border membrane in addition to being prevalent in the basal-lateral membrane. Adenylate cyclase had the same distribution pattern as (Na+ + K+)-ATPase, i.e. higher specific activity in basal-lateral membranes and present in brush border membranes. Adenylate cyclase in both membrane preparations was stimulated by parathyroid hormone, calcitonin, epinephrine, prostaglandins and 5'-guanylylimidodiphosphate. When the agonists were used in combination enhancements were additive. In contrast to the distribution of adenylate cyclase, guanylate cyclase was found in the cytosol and in basal-lateral membranes with a maximal specific activity (NaN3 plus Triton X-100) 10-fold that in brush border membranes. ATP enhanced guanylate cyclase activity only in basal-lateral membranes. It is proposed that guanylate cyclase, in addition to (Na+ + K+)-ATPase, be used as an enzyme "marker" for the renal basal-lateral membrane.
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PMID:Preparation of renal cortex basal-lateral and bursh border membranes. Localization of adenylate cyclase and guanylate cyclase activities. 1 97

Studies were carried out to determine if the receptors for parathyroid hormone, calcitonin, and prostaglandin E1 could be differentiated in renal cortex. Slices of rabbit renal cortex were incubated in buffer containing theophylline for 1 hr and then in fresh buffer with and without hormone for an additional period of 15 to 30 min. Parathyroid hormone caused a marked increase in 3',5'-AMP in both the tissue and the reaction medium. The maximal increase in 3',5'-AMP in response to prostaglandin E1 was similar to that of parathyroid hormone in the tissue but significantly less in the medium. The maximal response to calcitonin was less in both the tissue and the medium. Addition of 200 mug/ml trypsin to the first incubation abolished the subsequent response to parathyroid hormone in both the tissue and the reaction medium but did not affect the basal concentration of 3',5'-AMP or the response to calcitonin or prostaglandin E1. Controls were carried out to show that the lack of response to parathyroid hormone could not be attributed to hydrolysis of the hormone by residual trypsin. Slices were also homogenized after preincubation with and without trypsin and assayed for adenylate cyclase activity. Incubation with trypsin markedly diminished the increase in enzyme activity in response to parathyroid hormone but did not alter the basal activity or the response to calcitonin or sodium fluoride. The response to prostaglandin E1 was significantly increased. Combinations of any two or the three hormones at maximal concentrations caused an additive increase in adenylate cyclase activity. The results indicate that the receptors for parathyroid hormone, calcitonin and prostaglandin E1 in renal cortex are separate and the receptor for parathyroid hormone can be selectively hydrolyzed by proteolytic digestion.
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PMID:Selective proteolysis of the receptor for parathyroid hormone in renal cortex. 16 81

It has been shown that both parathyroid hormone (PTH) and calcitonin (CT) increase the concentration of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in skeletal tissue. Since these two hormones have opposing actions on bone resorption, it has been postulated that the cell types upon which the hormones act in skeletal tissue may be different. We have previously shown that osteoblasts and osteocytes contain adenylate cyclase responsive to both PTH and CT whereas the enzyme prepared from periosteum and marrow cells did not respond to either. To further examine the postulate, the effect of these hormones on the concentration of cyclic AMP was determined. Bovine PTH (5U/ml equal to 4.2 times 10-7M) significantly increased the concentration of cyclic AMP/mug DNA in periosteum, osteoblasts, and osteocytes but not in marrow cells. Porcine CT (0.5 U/ml equal to 8.0 mug/ml approximately equal to 3.0 times 10-6M) significantly increased the concentration of cyclic AMP/mug DNA in periosteum, osteoblasts, osteocytes, and marrow cells. Adenylate cyclase activity prepared from periosteum and marrow cells was re-examined using EGTA and DMSO to improve enzyme stability and activity. Wth these additions PTH (5 U/70 mul) increased activity of the preparation from periosteum, and CT (0.5 U/70 mul) increased activity from marrow cells and periosteum. These studies provide evidence that: 1) periosteum, osteoblasts, and osteocytes respond directly to both PTH and CT and 2) marrow cells respond to CT and not PTH.
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PMID:Cyclic 3', 5'-adenosine monophosphate levels in separated bone cells. 16 45

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.
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PMID:Selective proteolysis of the receptor for parathyroid hormone in skeletal tissue. 16 56

High affinity binding of 125I-labeled salmon calcitonin ([125I]SCT) and calcitonin-activated adenylate cyclase were detectable in renal plasma membranes from the rat. Addition of 5'-guanylyl-imidodiphosphate lowered the threshold for enzyme activation by peptide hormones. Renal plasma membranes from man, dog and cow contained little or no calcitonin-sensitive adenylate cyclase and showed no high affinity binding of [125I]SCT. High affinity binding sites were distributed during membrane fractionation in fractions where the specific activity of hormone-sensitive adenylate cyclase was greatest. Calcitonin binding and activation of the adenylate cyclase enzyme occurred at similar hormone concentrations. The relative potencies of calcitonin analogues were similar whether measured by competition for high affinity binding sites or by effect on adenylate cyclase. Low concentrations of Lubrol-PX, a nonionic detergent, did not affect catalytic function of the enzyme determined in the presence of sodium fluoride but caused parallel loss of high affinity [125I]SCT binding and hormonal sensitivity of the enzyme. This observation provided further evidence that interaction of calcitonin with specific receptors (identified with [125I]SCT binding) is essential for calcitonin activation of adenylate cyclase, but showed that catalytic activity of enzyme does not require functioning hormone receptors.
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PMID:Renal receptors for calcitonin: coordinate occurrence with calcitonin-activated adenylate cyclase. 16 26

Purification of pork renal cortex membranes yielded a particulate adenylate cyclase retaining good sensitivity to stimulation by parathyroid hormone and glucagon and a modest but significant response to porcine calcitonin. Treatment of this partially purified membrane fraction with 0.5% Lubrol PX and 5 mM NaF released adenylate cyclase activity into a fraction which was not sedimented by centrifugation for 20 min at 37,000 X g or for 2 hours at 100,000 X g and passed through a Millipore filter (0.22 mum pore). This solubilized adenylate cyclase was stimulated by porcine calcitonin and NaF but not by parathyroid hormone or glucagon. On gel filtration (Sephadex G-200) in the presence of 1mM dithiothreitol and 5mM NaF, the major portion of the adenylate cyclase activity eluted with the void volume of the column and showed 2.0-fold stimulation with 10 muM calcitonin. Binding of 125I-labeled porcine calcitonin was demonstrated in the 37,000 X g and the 100,000 X g supernatants. From 74 to 86% of the observed binding could be blocked by the addition of unlabeled porcine calcitonin to the reaction mixture. Addition of salmon calcitonin, parathyroid hormone, or glucagon blocked only 12 to 18% of the binding. The dose-response curves for inhibition of binding of iodinated calcitonin by unlabeled calcitonin and the activation of adenylate cyclase by the hormone each showed 50% maximal effect at a concentration between 4.5 and 8 muM porcine calcitonin and maximal effect at a concentration between 33 and 66 muM porcine calcitonin.
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PMID:Solubilization of calcitonin-responsive renal cortical adenylate cyclase. 17 Feb 64

Calcitonin, whatever its origin, produces a decrease in the renal tubular reabsorption of sodium, phosphate and calcium in man and in the rat. Renal receptors for calcitonin have been demonstrated in the membranes of rat tubular cells using 125I salmon calcitonin as a tracer. Hormone-receptor interaction initiates the activation of membrane adenyl cyclase. In the rat and in man, the kidney plays a major role in degradation of both human and salmon calcitonin. Plasma levels of immunoreactive calcitonin are high in chronic renal failure. The question of the physiological role of calcitonin on kidney function is still unsettled.
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PMID:Kidney and calcitonin. 17 May 50

Free flow electrophoresis was employed to separate renal cortical plasma membranes into luminal (brush border microvilli) and contraluminal (basal-lateral membrane) fractions. During the separation adenylate cyclase activity was found to parallel the activity of Na+-K+-activated ATPase, an enzyme which is present in contraluminal but not in luminal membranes. In the basal-lateral membrane fraction the specific activities of adenylate cyclase and Na+-K+-activated ATPase were 4.4 and 4.6 times greater, respectively, than in the brush border fraction. The adenylate cyclase of the basal-lateral membrane fraction was specifically stimulated by parathyroid hormone which maximally increased enzyme activity eightfold. The biologically active (1-34) peptide fragment of paratyhroid hormone produced a 350% increase in adenylate cyclase activity. In contrast, calcitonin, epinephrine and vasopressin maximally stimulated the enzyme by only 55, 35 and 30%, respectively. These results indicate that adenylate cyclase, specifically stimulated by parathyroid hormone, is distributed preferentially in the contraluminal region of the plasma membrane of renal cortical epithelial cells.
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PMID:Distribution of parathyroid hormone-stimulated adenylate cyclase in plasma membranes of cells of the kidney cortex. 17 37


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