Side chain oxidation of 1,25-dihydroxyvitamin D3 in the rat: Effect of removal of the intestine

Kumar, Rajiv; DeLuca, Hector F.

doi:10.1016/0006-291x(77)90719-7

Cited by 21 publications

(1 citation statement)

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“…A similar rapid disappearance of 1,25-(OH) 2 D3 from the plasma of two normal humans was described by Most likely, metabolic degradation accounts for much of the rapid disappearance of 1,25-(OH)2D 3 from the body. Side-chain cleavage of 1,25-(OH)2D3 occurs rapidly in chicks (28) as well as in rats (26,29). Perhaps a portion of the water-soluble radioactivity in the plasma extracts represents fragments of the side chain.…”

Section: Discussionmentioning

confidence: 99%

Pharmaeokinetics and Pharmacodynamics of 1,25-Dihydroxyvitamin D₃in the Chick

Bikle¹,

Peck²,

Holford³

et al. 1982

Endocrinology

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To relate the disposition kinetics of 1,25-dihydroxyvitamin D3 [1,25-(OH) 2 D 3 ] to its function, we injected a physiological dose of radiolabeled 1,25-(OH) 2 D 3 (84.6 pmol) into the wing veins of vitamin D-deficient chicks. The concentration of calcium-binding protein in duodenal mucosal cytosol, the concentration of 1,25-(OH)2D3 in plasma and duodenal mucosa, and the total radioactivity in bone, kidney, liver, muscle, pancreas, spleen, plasma, and duodenal mucosa were determined in individual chicks from 1-72 h later. The uptake of 1,25-(OH) 2 D 3 by the duodenal mucosa occurred quickly, reaching a peak concentration of 6.2 pmol/g wet wt at 3 h. This was followed by a rapid disappearance, the kinetics of which paralleled the terminal phase of plasma 1,25-(OH)2D3 disappearance. Intact 1,25-(OHhDa accounted for more than 75% of the total radioactivity in the duodenal mucosa for at least 36 h, but fell to 30% of the total radioactivity in plasma by 8 h. An unidentified metabolite which cochromatographed with 1,24,25-(OH)2D 3 appeared in the duodenal mucosa and plasma within 1 h after 1,25-(OH)2D3 administration. Its disposition paralleled that of 1,25-(OH)2D3 in the duodenal mucosa, but it disappeared from plasma more slowly than 1,25-(OH)2D 3 . We determined that a two-compartment model adequately described the disposition kinetics of 1,25-(OH) 2 D3 in the vitamin D-deficient chick. The a and /? half-lives for 1,25-(OH) 2 D 3 disappearance, as calculated from the model, were 0.5 and 6.4 h, respectively. The volumes of distribution of the two compartments in the model were calculated as 16.7 ml and 5.65 g wet wt, respectively. The parallel and rapid disappearance of radioactive label from plasma, liver, muscle, and spleen in contrast to the initial retention or accumulation of the label by duodenal mucosa, kidney, bone, and pancreas is consistent with the view that one compartment is comprised of tissues that contain specific 1,25-(OH) 2 D 3 receptors. In contrast to the rapid disappearance of 1,25-(OH) 2 D 3 from plasma and duodenum, the biological effects of 1,25-(OH) 2 D 3 were delayed and longer lasting. Calcium-binding protein was first detected in the duodenal mucosal cytosol at 6 h, reached a maximal concentration (1.15 fig/mg protein) at 18 h, and persisted at this level for at least 72 h despite the nearly complete disappearance of 1,25-(OH) 2 D 3 from the intestinal mucosa. (Endocrinology 111: 939, 1982) 1 ,25-DIHYDROXYVITAMIN D 3 [1,25-(OH) 2 D 3 ] is the fastest acting, most potent metabolite of vitamin D 3 known with respect to its action on bone and gut (1, 2). This metabolite is made from 25-hydroxyvitamin D 3 (25OHD3) in the kidney (3), from which it must be transported to the target tissues. The fate of 1,25-(OHhDs in the body clearly has relevance to its actions. Studies of 1,25-(OH) 2 D 3 metabolism in vitamin D-replete humans by Gray et al. (4) and Mawer et al. (5) were necessarily limited to sampling only the plasma compartment and excretory products. A less limited study of 1,25-(OH) 2...

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Section: Discussionmentioning

confidence: 99%

Pharmaeokinetics and Pharmacodynamics of 1,25-Dihydroxyvitamin D₃in the Chick

Bikle¹,

Peck²,

Holford³

et al. 1982

Endocrinology

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Vitamin D Endocrine System and Calcium and Phosphorus Homeostasis

Gross

Kumar

1992

Comprehensive Physiology

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The sections in this article are: Physiological Effects of Vitamin D and its Active Metabolites on Calcium and Phosphorus Homeostasis Sources of Vitamin D Transport of Vitamin D and its Metabolites in Plasma Metabolism of Vitamin D 3 to 25‐Hydroxyvitamin D 3 Metabolism of 25‐Hydroxyvitamin D 3 Regulation of the 25‐Hydroxyvitamin D 3 –1α‐Hydroxylase Enzyme Parathyroid Hormone Phosphorus Concentrations Calcium: Direct Effects 1,25‐Dihydroxyvitamin D 3 Calcitonin Hydrogen Ion Sex Steroids Glucocorticoids Pituitary Hormones Thyroid Hormone Pregnancy Catabolism of 1,25‐Dihydroxyvitamin D 3 Physiological Adaptations that Occur in Response to Changes in Serum Calcium and Phosphate Concentrations Hypocalcemia and Hypercalcemia Hypophosphatemia and Hyperphosphatemia Pathophysiology and Physiology of the 1,25‐Dihydroxyvitamin D 3 System Mechanisms of Action of 1,25‐Dihydroxyvitamin D 3 1,25‐Dihydroxyvitamin D 3 in the Intestine Processes in the Cell That Are Mediated by 1,25‐Dihydroxyvitamin D 3 Intestinal Brush Border Events Induced by 1,25‐Dihydroxyvitamin D 3 Events at the Contraluminal Border Effects of 1,25‐Dihydroxyvitamin D 3 on the Intestinal Cell 1,25‐Dihydroxyvitamin D 3 in the Kidney

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