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)

This study investigated the sex- and age-related alterations in calcium homeostasis in 39- to 82-week-old rats raised from weaning on a vitamin D deficient (-D) diet. It was found that vitamin D deprivation decreased the life span of male, but not female, rats. Female -D animals exhibited a steady increase in serum calcium with age from 39 to 82 weeks, although circulating calcium of -D animals never reached normocalcemic levels. There was no attenuation of the secondary hyperparathyroidism. Serum calcium of -D males was significantly lower than that of age-matched females at all ages when sufficient males were alive to make the comparison. Serum parathyroid hormone levels were decreased in -D females when serum calcium was elevated to hypercalcemic levels by calcium injection. Similarly, administration of vitamin D3 or 1,25-dihydroxyvitamin D3 elevated serum calcium and depressed parathyroid hormone in 14- and 22-month-old -D females. These animals also exhibited increased intestinal calcium binding protein content. Administration of vitamin D3 or dihydroxyvitamin D3 repaired renal adenylate cyclase refractoriness to parathyroid hormone. The sex- and diet-related alterations in serum phosphorus that were found at earlier ages disappeared by 67 weeks of age. Serum calcitonin was elevated in mature and aging +D males and females and -D females relative to younger animals. In -D males, calcitonin levels were less markedly elevated. The results of this study indicate that there are several important sex differences related to the regulation of calcium homeostasis in mature and aging rats. In addition, it was found that mature (14 month) and old (22 month) chronically -D female rats were able to respond to repletion with dihydroxyvitamin D3 or vitamin D within 10 days.
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PMID:Effects of long-term vitamin D deficiency and response to vitamin D repletion in the mature and aging male and female rat. 632 33

The effect of PGE2 on the conversion of 25-hydroxyvitamin D3 (25 OH D3) to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) by isolated renal tubules from vitamin D deficient chicks was studied under a variety of experimental conditions. In the absence of added vitamin D metabolites, PGE2 (2 x 10(-6)M) caused an immediate inhibition of formation of 1,25-(OH)2D3, followed by a delayed stimulation, apparent after 15 h exposure to PGE2. Pretreatment of the tubules with 1,25-(OH)-2D3 prevented the immediate inhibitory action of PGE2, and allowed the stimulation to be apparent after 4 h exposure to PGE2. The cyclic nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine (IBMX) significantly stimulated the formation of 1,25-(OH)-2D3. PGE2 significantly inhibited 1,25-(OH)2D3 formation in tubules which had been stimulated by IBMX. PGE2 stimulated the adenylate cyclase activity in a crude particulate fraction from the chick kidney, and raised cyclic adenosine 3', 5'-monophosphate (cyclic AMP) levels in the renal tubules. It is concluded that PGE2 can either stimulate or inhibit 1,25-(OH)2D3 formation in chick renal tubules. The stimulatory effect may be partly due to elevation of cyclic AMP. The mechanism of the inhibitory effect requires further investigation.
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PMID:Biphasic action of prostaglandin E2 on conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 in chick renal tubules. 632 79

The in vitro incubation of chick renal cells with parathyroid hormone (PTH) resulted in the inhibition of Na+-dependent phosphate uptake when the cells were isolated from 1,25-dihydroxycholecalciferol 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]-repleted chicks but not when the cells came from vitamin D-deficient animals. Na+-independent phosphate and Na+-dependent alpha-methylglucoside uptakes were not affected by PTH and the vitamin D status of the bird. The activation of chick renal cell adenylate cyclase by PTH was significantly blunted when the enzyme was from vitamin D-deficient animals relative to the activation of the enzyme from repleted cockerels. This alteration was due to a change in maximum velocity of the system rather than an effect on the affinity for hormone. The response of adenylate cyclase to other hormones, e.g., prostaglandin E2, and activators, e.g., 5' -guanylyl-imidodiphosphate and forskolin, was not affected by the vitamin D status of the animal. PTH had little effect in activating protein kinase in cells from vitamin D-deficient chicks. In cells from vitamin D-sufficient birds, PTH caused a fourfold increase in adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. Dibutyryl cAMP inhibited Na+-dependent phosphate uptake by cells from 1,25-(OH)2D3-repleted animals, but the cyclic nucleotide had no effect on phosphate uptake in cells from vitamin D-depleted chicks. This finding suggests that the loss of PTH receptor sites known to be concomitant with the secondary hyperparathyroidism associated with vitamin D deficiency is only a partial explanation for the failure of PTH to inhibit phosphate uptake in cells from vitamin D-deficient animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Responses of chick renal cell to parathyroid hormone: effect of vitamin D. 654 26

The effect of prostaglandin E2 on accumulation in plasma of 1 alpha,25-dihydroxy[3H]vitamin D3 from 25-hydroxy[3H]vitamin D3 was studied in vivo using vitamin D-deficient thyroparathyroidectomized rats. Intra-arterial infusion of 10-50 micrograms of prostaglandin E2/h caused a significant stimulation of 1 alpha,25-dihydroxy[3H]vitamin D3 production. No significant changes in plasma Ca2+ and Pi concentrations or urinary cyclic AMP excretion were observed after prostaglandin E2 infusion. Theophylline did not enhance the effect of a submaximal dose of prostaglandin E2 on 1 alpha,25-dihydroxy[3H]vitamin D3 production. These data indicate that prostaglandin E2 stimulates plasma accumulation of 1 alpha,25-dihydroxy[3H]vitamin D3 independent of the adenylate cyclase/cyclic AMP system, and suggest that prostaglandin E2 has a modulatory role in the regulation of 25-hydroxyvitamin D3 1 alpha-hydroxylase in the kidney.
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PMID:Stimulatory effect of prostaglandin E2 on 1 alpha,25-dihydroxyvitamin D3 synthesis in rats. 658 Sep 3

The effects of 1 alpha (OH)vitamin D3 [1 alpha (OH)D3] and 24,25(OH)2vitamin D3 [24,25(OH)2D3] on the phosphaturic action of parathyroid hormone (PTH) were studied in two groups of parathyroidectomized (PTX) rats. In group 1, PTX PTH-infused rats received intravenous 1 alpha (OH)D3, and in group 2, PTX PTH-infused rats received intravenous 24,25(OH)2D3. PTX PTH-infused rats served as controls. The effects of both vitamin D metabolites on renal PTH-activated adenylate cyclase (AC) were studied in vitro. In group 1, PTH increased fractional excretion of phosphate (CP/CIn) from 0.045 +/- 0.012 (+/- SE) to 0.263 +/- 0.011 (P less than 0.005). 1 alpha (OH)D3 failed to influence this response. In group 2, PTH increased CP/CIn from 0.055 +/- 0.008 to 0.289 +/- 0.027 (P less than 0.005). 24,25(OH)2D3 reduced the PTH-induced rise in CP/CIn from 0.289 +/- 0.027 to 0.192 +/- 0.021 (P less than 0.01) and decreased the urinary excretion of adenosine 3',5'-cyclic monophosphate. In vitro, 24,25(OH)2D3 blunted the PTH-activated AC, whereas 1 alpha (OH)D3 had no effect. These results show that 24,25(OH)D3, similar to two other 25(OH) metabolites of vitamin D-25(OH)vitamin D3 and 1,25(OH)2vitamin D3-suppresses the phosphaturic action of PTH, whereas 1 alpha(OH)D3, which is devoid of a 25(OH) group, lacks this effect. This suggests that a 25(OH) group is a prerequisite for the antiphosphaturic effect of vitamin D, whereas the 1 alpha (OH) group is not essential for this action.
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PMID:Renal effect of vitamin D metabolites: evidence for the essential role of the 25(OH) group. 660 55

To further characterize the mechanisms by which 25(OH) vitamin D3 (25(OH)D3) and 1.25(OH)2 vitamin D3 (1,25(OH)2D3) suppress the phosphaturic action of parathyroid hormone (PTH) we have studied the effects of cycloheximide (cyclohex), a protein synthesis inhibitor, on the interaction between PTH and vitamin D metabolites in parathyroidectomized (PTX) rats, both in vivo and in vitro experiments. In clearance studies PTX PTH-infused rats were pretreated with cyclohex 2 h before the administration of vitamin D. In control, PTX PTH-infused rats not pretreated with cyclohex, the administration of 25(OH)D3 and 1,25(OH)2D3 was associated with a fall in fractional excretion of phosphate (CP/CIN) from 0.30 +/- 0.05 to 0.16 +/- 0.02 and from 0.31 +/- 0.05 to 0.13 +/- 0.01 (P less than 0.005) respectively. Cyclohex-pretreated PTX PTH-infused rats failed to respond to both 25(OH)D3 and 1,25(OH)2D3, and CP/CIN, which rose after PTH, remained 0.32 +/- 0.05 and 0.29 +/- 0.03 respectively. In vitro, both 25(OH)D3 and 1,25(OH)2D3 inhibited the PTH-induced activation of adenylate cyclase in the renal isolated membrane fractions. Pretreatment with cyclohex abolished this effect of vitamin D metabolites. These results show that cyclohex blocks the antiphosphaturic effects of both 25(OH)D3 and 1,25(OH)2D3 but does not alter the response to PTH. These findings are consistent with the possibility that the acute renal action of vitamin D depends on de novo synthesis of protein.
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PMID:Blockade of the renal tubular effects of vitamin D by cycloheximide in the rat. 668 70

Renal cells from Vitamin D-deficient and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-repleted chicks were isolated by a collagenase-hyaluronidase procedure. Exclusion of trypan blue and respiratory measurements indicate that the cells were functionally intact and metabolically active. The uptakes of phosphate and alpha-methylglucoside were stimulated markedly by Na+ in the extracellular medium. Phosphate uptake in the presence of Na+ was saturable with respect to phosphate concentration; half-maximal activity was obtained with approximately 0.2 mM. Three hours after 1,25-(OH)2D3 was injected into vitamin D-deficient chicks the Na+-dependent phosphate uptake by the isolated cells had increased about 40%, i.e., 2.00 compared with 1.44 nmol.min-1.mg protein-1. Phosphate uptake in the presence of K+ in the extracellular medium and alpha-methylglucoside uptake in the presence or absence of Na+ were unchanged. In a secondary response found 17 h after 1,25-(OH)2D3 injection, Na+-dependent phosphate uptake decreased. Serum concentrations of phosphorus and calcium were not measurably changed in the 3-h repleted bird, but both levels were increased 17 h after treatment. Administration of phosphate into vitamin D-deficient chicks, so that the serum concentration of phosphorus was raised to that of the 17-h 1,25-(OH)2D3 repleted animal, effected a comparable decrease in phosphate uptake. Serum calcium levels were not altered by this treatment. The actions of parathyroid hormone in stimulating adenylate cyclase and in inhibiting phosphate uptake were notably blunted in the vitamin D-deficient chick. Sensitivity to parathyroid hormone was not restored until several days after 1,25-(OH)2D3 repletion. These findings suggest that the initial response to 1,25-(OH)2D3, to increase renal phosphate uptake, and the secondary response, to decrease phosphate uptake, were by parathyroid hormone-independent processes. The results also indicate that the isolated renal cell represents an excellent model for studying the mechanism by which 1,25-(OH)2D3 regulates phosphate transport in the kidney.
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PMID:Effects of 1,25-(OH)2D3 administered in vivo on phosphate uptake by isolated chick renal cells. 689 66

1. Plasma membranes were prepared from parathyroid adenomas in patients with primary hyperparathyroidism and from hyperplastic glands obtained from patients with chronic renal insufficiency. The basal and isoproterenol- or sodium fluoride-stimulated adenylate cyclase activities were measured in membranes in the presence of several vitamin D3 metabolites. 2. 24,25-Dihydroxycholecalciferol (10 and 1000 pmol/l) decreased isoproterenol- and sodium fluoride-stimulated adenylate cyclase activities in membranes prepared from parathyroid glands. 1,25-Dihydroxycholecalciferol (1000 pmol/l) inhibited the isoproterenol-stimulated adenylate cyclase activity. 25-Hydroxycholecalciferol and vitamin D3 had no effect on adenylate cyclase activities. Basal adenylate cyclase activity was not affected by any of th vitamin D3 metabolites tested. 3. These results indicate that 24,25-dihydroxycholecalciferol inhibits the isoproterenol- and sodium fluoride-stimulated adenylate cyclase activities in parathyroid tissues. Such an inhibition could explain the very rapid decrease in parathyroid hormone secretion after 24,25-dihydroxycholecalciferol administration that has been previously reported.
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PMID:Human parathyroid gland adenylate cyclase activity: inhibition by 24,25-dihydroxycholecalciferol in vitro. 697 85

The components of calcium and magnesium balance and the factors responsible for the maintenance of the serum concentration of these cations are reviewed. Within this framework, the causes and treatment of disturbances of the serum concentration are discussed. Hypercalcemia is usually a reflection of increased bone resorption and/or gut absorption with the kidney playing a secondary role. Hypocalcemia is usually due to either a disturbance in the parathyroid hormone-adenylate cyclase system or a disturbance in vitamin D metabolism. As vitamin D is required for expression of the action of PTH at bone and as PTH is a prime regulator of vitamin D metabolism, the absence of either component results in important disturbances in calcium balance. In contrast to calcium homeostasis, the kidney plays a major role in the determination and regulation of serum magnesium. The major causes of hypermagnesemia therefore are associated with loss of renal function, and hypomagnesemia is frequently due to renal magnesium wasting.
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PMID:Disorders of calcium and magnesium homeostasis. 703 37

The time course of change in plasma calcium levels and renal metabolism of 25-hydroxyvitamin D3 [25(OH)D3] was investigated in chicks maintained on a vitamin D-deficient diet for 4 weeks. Plasma calcium concentrations dropped sharply between the 7th and 14th day of the feeding period. Renal 25(OH)D3-1 alpha-hydroxylase activity was reciprocally enhanced concurrently with the decrease in plasma calcium levels. The elevated activity of 1 alpha-hydroxylase had declined significantly by the 21st and 28th days in spite of the more severe hypocalcemia. When graded amounts of vitamin D3 were administered to the chicks maintained on this diet for 14 or 28 days, there were considerable differences in the change of plasma calcium levels and 25(OH)D3 metabolism induced by vitamin D3 administration between the 14-day and 28-day birds. The minimal dose levels of vitamin D3 to completely suppress renal 1 alpha-hydroxylase activity were 25 micrograms in the 14-day, and 2.5 mg in the 28-day birds. These differences were not observed between the 14-day and 28-day birds when 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] was administered. Renal adenylate cyclase activity induced by parathyroid hormone (PTH) was much lower in the 28-day chicks than that in 1-day-old and the 14-day birds. These results are explained by the hypersecretion of PTH and the subsequent refractoriness of the target organs in severe vitamin D deficiency. Plasma calcium levels per se did not appear to be a major factor in the regulation of 25(OH)D3 metabolism.
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PMID:Regulation and its refractoriness of 25-hydroxyvitamin D3 metabolism in vitamin D deficiency. 732 Jul 68


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