Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An experiment was carried out to investigate the effects of age of laying hens (young = 22 wk vs old = 120 wk) in maintaining Ca homeostasis during periods of Ca depletion then repletion with Ca. Plasma Ca and P, tibia breaking strength and percentage ash, renal 25-hydroxycholecalciferol-1-hydroxylase (1 alpha-hydroxylase), and parathyroid hormone (PTH)-stimulated adenylate cyclase activities were studied during 28 d of Ca depletion on a .08% Ca diet (LC) and 28 d of Ca repletion on a 3.75% Ca diet (HC). When laying hens on a HC diet were placed on a LC diet, plasma Ca and P, tibia breaking strength and ash percentage, and renal PTH-dependent adenylate cyclase activity were significantly depressed, but renal 1 alpha-hydroxylase activity was significantly stimulated. These changes were greater in the young hens than in the older hens; therefore an interaction between age and dietary Ca was found. These changes were of a lesser magnitude at 28 d of Ca depletion, probably due to the cessation of egg laying and to the desensitization of hormone-mediated function. 1 alpha-Hydroxylase activity was significantly less during the repletion period. The age effect was most pronounced for 1 alpha-hydroxylase, with the younger birds expressing significantly higher activity and ability to respond to hypocalcemia. There was a significant increase in kidney weights in Ca-deficient groups at 14 and 28 d of Ca depletion. It is concluded that younger hens have greater adaptive responses to Ca restriction than do older hens.
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PMID:Calcium homeostasis in the laying hen. 1. Age and dietary calcium effects. 781 33

Avian kidney function adapts during reproduction to provide the calcium required for eggshell formation. Adaptive changes in kidney function are 1) increased parathyroid hormone (PTH)-dependent adenylate cyclase activity; 2) elevated numbers of PTH receptors; and 3) increased synthesis of 1,25-dihydroxycholecalciferol. Because exogenous estrogen mimics these changes, this study explored the physiological role of estrogen in the regulation of kidney function by altering egg-laying status or levels of estradiol. In hens, treatment with the coccidiostatic drug, nicarbazin, led to cessation of egg laying with maintenance of the reproductive tract and of plasma estradiol and calcium. The PTH-dependent adenylate cyclase activity remained elevated (upregulated). However, when molting was induced by altering the photoperiod and diet, plasma estradiol, plasma calcium, and renal PTH-dependent adenylate cyclase activity all decreased. The depressed responsiveness to PTH was restored by administration of estradiol either during the molt or upon return to egg laying following the molt. When the estrogen antagonist, tamoxifen, was administered to laying hens, reproduction ceased and the PTH-dependent adenylate cyclase activity of renal membranes was decreased. In all three groups of nonlaying birds, the activity of kidney 25-hydroxycholecalciferol-1-hydroxylase was markedly decreased relative to that of laying hens irrespective of the amount of plasma estradiol. It was concluded that estrogen regulates the PTH-dependent adenylate cyclase system of avian kidney, whereas the activity of the 25-hydroxycholecalciferol-1-hydroxylase of kidney and thus, the synthesis of 1,25-hydroxycholecalciferol may be governed at least in part by the regulation of renal receptors for PTH by estrogen.
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PMID:Adaptation of the kidney during reproduction: role of estrogen in the regulation of responsiveness to parathyroid hormone. 839 92

The 25-hydroxyvitamin D3 1alpha-hydroxylase, also referred to as CYP27B1, is a mitochondrial cytochrome P450 enzyme that catalyzes the biosynthesis of 1alpha, 25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) from 25-hydroxyvitamin D3 in renal proximal tubular cells. Recently, human, mouse, and rat CYP27B1 cDNA have been cloned, however the gene regulation has not been fully elucidated. In the present study, porcine CYP27B cDNA was cloned, and the effects of cAMP and vitamin D3 on the regulation of CYP27B1 mRNA expression in LLC-PK1 cells were examined. PCR cloning revealed that porcine CYP27B1 cDNA consisted of 2316 bp, encoding a protein of 504 amino acids. The deduced amino acid sequence showed over 80% identity to the human, mouse, and rat enzyme. LLC-PK1 cells were incubated with humoral factors, and expression of CYP27B1 mRNA was measured by a quantitative reverse transcription-PCR. At the completion of 3-, 6-, 12-, and 24-h incubations, 500 micromol/L 8-bromo-cAMP had significantly increased CYP27B1 mRNA expression (260 to 340%). The adenylate cyclase activator forskolin at 50 micromol/L also had a stimulatory effect at 6 h (190%). Moreover, the protein kinase A inhibitor H-89 reduced the cAMP effect. On the other hand, 1alpha,25(OH)2D3 had no effect on CYP27B1 mRNA expression at 10 and 100 nmol/L, whereas expression of 25-hydroxyvitamin D3 24-hydroxylase (CYP24) mRNA was markedly increased by 1alpha,25(OH)2D3. These findings suggest that LLC-PK1 cells express CYP27B1 mRNA, and that cAMP is an upregulating factor of the CYP27B1 gene in vitro.
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PMID:Cloning of porcine 25-hydroxyvitamin D3 1alpha-hydroxylase and its regulation by cAMP in LLC-PK1 cells. 1023 81