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 vitamin D metabolism by the kidney is now known to be multifactorial. Three regulatory factors are discussed: 1,25(OH)2D3 itself; parathyroid hormone, and phospate. The influence of 1,25(OH)2D3 probably depends on new protein synthesis, while the mode of action of phosphate is unknown. Parathyroid hormone is not essential for regulation but may have an important biological role. The direction of its effect varies, perhaps due to a complex interrelation of changes in calcium and phosphorus metabolism and the level of kidney adenyl cyclase activity.
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PMID:Regulation of vitamin D: an evolutionary view. 21 35

Bovine parathyroid hormone (PTH), dibutyryl cAMP, and calcium each induce similar metabolic changes in isolated bone cells. PTH and calcium, but not dibutyryl cAMP, result in desensitization of osteoclastic and osteoblastic bone cells to PTH. In osteoblastic cells, calcium effects are specific for PTH receptor.adenylate cyclase complexes and responsiveness to other hormones is not reduced while in osteoclastic cells, small effects of high calcium on prostaglandin E1- and epinephrine-inducible cAMP accompany the large decreases seen in cAMP response to PTH. The membrane effects of calcium and of PTH appear to be independently regulated as PTH-induced desensitization can be initiated in the absence of calcium. In addition, calcium effects on PTH-sensitive adenylate cyclase follow a different calcium dose-response than PTH-like metabolic changes. These results suggest that the effect of calcium on the membrane is not directly related to its induction of PTH-like metabolic changes. A possible role of calcium as an in vivo regulator of bone cell sensitivity to PTH is discussed.
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PMID:Induction of metabolic changes and down regulation of bovine parathyroid hormone-responsive adenylate cyclase are dissociable in isolated osteoclastic and osteoblastic bone cells. 21 43

We have examined the effect of parathyroid hormone (PTH) on the adenylate cyclase activity of newborn osteopetrotic rat calvaria, to study a possible molecular basis for the reduced response of this mutant to PTH. Phenotypically normal littermates served as controls. We also measured the effect of PTH on kidney adenylate cyclase activity and on lactic acid accumulation in short term cultures of calvaria. PTH stimulated calvarial adenylate cyclase activity in a dose-dependent manner in both mutant rats and normal littermates. Lactic acid production was also enhanced by PTH, and no significant difference between mutants and normal littermates was observed. These findings indicate that the reduced response of the young osteopetrotic rats to PTH is not due to an absence of PTH receptors coupled to adenylate cyclase.
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PMID:Parathyroid hormone stimulation of adenylate cyclase activity and lactic acid accumulation in calvaria of osteopetrotic (ia) rats. 21 27

The two first steps of the renal cellular action of parathyroid hormone and of calcitonin are the hormonal binding onto specific receptors and the stimulation of adenylate cyclase by the hormone-receptor complex producing an increase in the intra-cellular concentration of 3'-5' cyclic adenosine monophosphate (cyclic AMP). Specific glomerular and tubular receptors for parathyroid hormone have been demonstrated using either tritiated parathyroid hormone or an indirect technique with 125 I labelled specific antibodies. Tubular receptors are localized both in the proximal and distal segments of the nephron. Parathyroid hormone stimulates glomerular and tubular adenylate cyclase. The main unsolved problem is the difficulty for demonstrating high affinity binding sites and stimulation of adenylate cyclase at low physiological concentrations of parathyroid hormone. In man, administration of parathyroid hormone produces a marked increase in the urinary excretion of cyclic AMP chiefly concerning its nephrogenous fraction. The peak of excretion is early and precedes the decrease in phosphate tubular reabsorption. Tubular receptors for calcitonin have been demonstrated using 125 I labelled salmon calcitonin. Calcitonin stimulates renal adenylate cyclase in only some segments of the nephron allowing receptors for calcitonin to be localized in the wide ascending branch of Henle's loop and the initial part of the convoluted distal tubule. In the presence of guanylnucleotides, binding of calcitonin onto its receptors and activation of adenylate cyclase are observed in the range of physiological concentrations of calcitonin in the rat. In man, administration of calcitonin produces a moderate increase in the urinary excretion of cyclic AMP coming from a non renal tissue.
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PMID:[Renal receptors of parathyroid hormone and calcitonin (author's transl)]. 21 63

A series of clinical studies suggest that the primary defect underlying pseudohypoparathyroidism is an abnormality of the parathyroid hormone-receptor-adenylate cyclase complex of the renal cortical cell plasma membrane. In the present study we compared parathyroid hormone-stimulated adenylate cyclase activity in membrane preparations from the renal cortex of three controls and a patient with pseudohypoparathyroidism. In the pseudohypoparathyroid preparation the Km for ATP was significantly greater and parathyroid hormone elicited markedly diminished adenylate cyclase activity at a subsaturating concentration of ATP. In contrast, the dose-response effect of enzyme activity to parathyroid hormone was the same in the control preparations, and that of the pseudohypoparathyroidism kidney, at a saturating concentration of ATP. The apparent alteration in enzyme kinetics, however, was normalized upon addition of guanosine 5'-triphosphate to the reaction mixtures. These results indicate that the defect in the parathyroid hormone-receptor-adenylate cyclase complex of the renal cell membranes, in our patient with pseudohypoparathyroidism, is an abnormal nucleotide receptor site of decreased activity. Such a defect may result in partial uncoupling of the parathyroid hormone receptor and adenylate cyclase, rendering the organ refractory to hormonal stimulation.
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PMID:Altered activity of the nucleotide regulatory site in the parathyroid hormone-sensitive adenylate cyclase from the renal cortex of a patient with pseudohypoparathyroidism. 21 26

Rats fed a diet deficient in vitamin D were found to exhibit a refractory cyclic AMP response of kidney slices to parathyroid hormone and a marked decrease in membrane parathyroid hormone-dependent adenylate cyclase activity. Both the characteristic calcium deficiency (hypocalcemia) and secondary elevation of circulating parathyroid hormone appeared before the first noticeable decrease in hormone-dependent enzyme activity. After repletion of D-deficient rats with vitamin D2, we found that serum calcium and parathyroid hormone were both restored to normal levels before the depressed enzyme response to the hormone was reversed. Moreover, infusion of parthyroid hormone into vitamin D-replete rats led to a marked reduction in parathyroid hormone-dependent adenylate cyclase activity, which was partly restored to control level 3 hours after discontinuing the hormone infusion. Taken as a whole, this study suggests that the elevated endogenous parathyroid hormone in the vitamin D-deficient rat is involved in the "down-regulation" of renal cyclic AMP responsiveness to the hormone. However, these experiments do not rule out the possibility that calcium deficiency and/or vitamin D per se participate in the regulation of the renal cyclic AMP response to parathyroid hormone.
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PMID:Regulation of the receptor-mediated cyclic AMP response of kidney to parathyroid hormone in the vitamin D-deficient rat. 21 92

We have previously shown that bone cells possess glucocorticoid receptors and that, in addition to being inhibitory to cell growth, glucocorticoid treatment potentiates the ability of parathyroid hormone (PTH) to stimulate cyclic AMP (cAMP) formation. This study extends those observations to specific subpopulations of bone cells and explores the mechanism of the cAMP augmentation. Subpopulations of cultured bone cells derived from 20-d-old fetal rat calvaria were enriched for "osteoblast-like" (OB) and "osteoclast-like" (OC) cells by sequential collagenase digestion. OC cells released during the first 30 min of collagenase digestion were characterized by low alkaline phosphatase activity, a cAMP response to salmon calcitonin (CT), but only a small cAMP response to bovine PTH. In contrast, OB cells released between 30 and 120 min of collagenase digestion, possessed high alkaline phosphatase activity, responded with a large cAMP rise to PTH, but exhibited no response to CT. Glucocorticoid receptors, with similar properties, were demonstrated in both populations (K(d) congruent with 5 nM, N(maximum) congruent with 400 fmol/mg cytosol protein). Dexamethasone equivalently inhibited cell growth and alkaline phosphatase activity in both populations. Dexamethasone potentiation of cAMP generation occurred after PTH but not CT stimulation. A greater enhancement of cAMP generation observed in OB cells appears to result from two glucocorticoid actions: (a) stimulation of adenylate cyclase and (b) inhibition of phosphodiesterase. Only the latter mechanism was found in OC cells. Dexamethasone-treated cells showed an increase in both sensitivity and maximal response of cAMP to PTH. The possible relationship of these actions to the mechanism of glucocorticoid-induced osteopenia is discussed.
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PMID:Glucocorticoid receptors and actions in subpopulations of cultured rat bone cells. Mechanism of dexamethasone potentiation of parathyroid hormone-stimulated cyclic AMP production. 22 Feb 82

To investigate the role of parathyroid hormone (PTH) and(or) an intrinsic renal tubular reabsorptive defect for phosphate in mice with hereditary hypophosphatemic rickets, we performed clearance and micropuncture studies in hypophosphatemic mutants and nonaffected littermate controls. Increased fractional excretion of phosphate in mutants (47.2+/-4 vs. 30.8+/-2% in controls) was associated with reduced fractional and absolute reabsorption in the proximal convoluted tubule and more distal sites. Acute thyropara-thyroidectomy (TPTX) increased phosphate reabsorption in both mutants and controls with a fall in fractional phosphate excretion to congruent with7.5% in both groups indicating that PTH modified the degree of phosphaturia in the intact mutants. Absolute reabsorption in the proximal tubule and beyond remained reduced in the mutants, however, possibly because of the reduced filtered load. Serum PTH levels were the same in intact mutants and normals as was renal cortical adenylate cyclase activity both before and after PTH stimulation. To evaluate the possibility that the phosphate wasting was caused by an intrinsic tubular defect that was masked by TPTX, glomerular fluid phosphate concentration was raised by phosphate infusion in TPTX mutants to levels approaching those of control mice. Phosphate excretion rose markedly and fractional reabsorption fell, but there was no change in absolute phosphate reabsorption in either the proximal tubule or beyond, indicating a persistent reabsorptive defect in the absence of PTH. We conclude that hereditary hypophosphatemia in the mouse is associated with a renal tubular defect in phosphate reabsorption, which is independent of PTH and therefore represents a specific intrinsic abnormality of phosphate transport.
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PMID:Evidence for an intrinsic renal tubular defect in mice with genetic hypophosphatemic rickets. 22 35

Cholera toxin, through adenylate cyclase activation reproduced cyclic AMP-mediated effects of thyroid-stimulating hormone (TSH) in dog thyroid slices, i.e. protein iodination, [1-14C]glucose-oxidation and hormone secretion. Iodide and carbamylcholine decreased the cyclic AMP accumulation induced by cholera toxin as well as by TSH, which supports the hypothesis of an action of these agents beyond the steps of hormone-receptor and receptor-adenylate cyclase interaction. Cooling to 20 degrees C did not impair the TSH induced cyclic AMP accumulation in thyroid slices, but completely suppressed the cholera toxin effect. This observation has been extended to other hormones and target tissues, such as the parathyroid hormone (PTH) (kidney cortex), adrenocorticotropic hormone (ACTH) (adrenal cortex) and luteinizing hormone (LH) (ovary systems). As in thyroid, cooling dissociated the cholera toxin and hormonal effects on cyclic AMP accumulation. In homogenate, cooling decreased cyclic AMP generation in the presence of cholera toxin but at 20 degrees C and 16 degrees C a cholera toxin stimulation was still observed. These results bear strongly against the hypothesis that the glycoprotein hormones TSH and LH acetivate adenylate cyclase by a mechanism identical to cholera toxin.
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PMID:Dissociation by cooling of hormone and cholera toxin activation of adenylate cyclase in intact cells. 22 51

Lithium treatment of humans and animals has been associated with adverse effects on bone and mineral metabolism. In order to determine whether lithium was altering the skeletal response to parathyroid hormone, we incubated bone rudiments for 5 days in the presence or absence of the drugs. Lithium had no effect on either parathyroid hormone-induced cyclic AMP generation or 45Ca release from the bone rudiments. The data are consistent with the hypothesis that the skeletal effects of lithium are not mediated via inhibition of the parathyroid hormone-adenyl cyclase-cyclic AMP system.
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PMID:Effect of lithium on parathyroid hormone-induced calcium release from bone rudiments. 22 5


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