Calcium, absorption intracellular

The steroid hormone 1,25-dihydroxy vitamin D3 (calcitriol) slowly increases both intestinal calcium absorption and bone resorption, and is also stimulated through low calcium levels. In contrast, calcitonin rapidly inhibits osteoclast activity and thus decreases serum calcium levels. Calcitonin is secreted by the clear cells of the thyroid and inhibits osteoclast activity by increasing the intracellular cyclic AMP content via binding to a specific cell surface receptor, thus causing a contraction of the resorbing cell membrane. The biological relevance of calcitonin in human calcium homeostasis is not well established. 

In addition to its role in regulating calcium homeostasis, vitamin D is required for the intestinal absorption of calcium. Synthesis of the intracellular calciumbinding protein, calbindin, required for calcium absorption, is induced by vitamin D, which also affects the permeability of the mucosal cells to calcium, an effect that is rapid and independent of protein synthesis. 

Copper absorption appears to occur through both a rapid, low-capacity system, and a slower, high-capacity system, which may be similar to the two processes seen with calcium absorption. Inactivating mutations in the gene encoding an intracellular copper ATPase have been shown to be responsible for the failure of intestinal copper absorption in Menkes disease. 

With the isolated perfused duodenum, there is a rapid increase in calcium transport in response to the addition of calcitriol to the perfusion medium. Isolated enterocytes and osteoblasts also show a rapid increase in calcium uptake in response to calcitriol. It is not associated with changes in mRNA or protein synthesis, but seems to be because of recruitment of membrane calcium transport proteins from intracellular vesicles to the cell surface. It is inhibited by the antimicrotubule compound colchicine. It can only be demonstrated in tissues from animals that are adequately supplied with vitamin D in vitamin D-deficient animals, the increase in intestinal calcium absorption occurs only more slowly, together with the induction of calbindin. 

Induction of Calbindin-D In response to calcitriol administration, there is an increase in mRNA synthesis and then in the synthesis of calbindin-D in intestinal mucosal cells, which is correlated with the later and more sustained increase in calcium absorption. In vitamin D-deficient animals, there is no detectable calbindin in the intestinal mucosa, whereas in animals adequately provided with vitamin D, it may account for 1 % to 3% of soluble protein in the cytosol of the colunmar epithelial ceils. Although the rapid response to calcitriol is an increase in the permeability of the brush border membrane to calcium, the induction of calbindin permits intracellular accumulation and transport of calcium. The rapid increase in net calcium transport in tissue from vitamin D-replete animals is presumably dependent on the calbindin that is already present in deficient animals, there can be no increase in calcium transport until sufficient calbindin has accumulated to permit intracellular accumulation, despite the increased permeability of the brush border. 

NaCIO is an acknowledged novel absorption enhancer for ampicillin sodium [99], glycyr-rhizin [100,101], gentamicin [102], phenoxymethyl penicillin [103], cefoxitin sodium [104,105], and acyclovir [106], Takahashi et al. [107] reported that the enhanced membrane permeability of phenolsulfonphthalein depends on the disappearance kinetics of CIO from the loop and its calcium ion sequestration capacity. The enhancing mechanisms of NaCIO are proposed to be involved in (1) Ca2+ sequestration, (2) increase in pore size and solvent drag, (3) interaction with membrane proteins and lipids, and (4) increase in the intracellular calcium level [104,105,108-111],... 

Q7 Calcium is present in both intracellular fluid (ICF) and ECF, but the concentration in the ECF is twice as high as that in the ICF. Calcium is found in both ionized and bound forms, and Ca2+ homeostasis is mainly controlled by parathyroid hormone, which increases absorption of calcium in the intestine and reabsorption in the nephron. Calcitonin also affects ECF calcium concentration by promoting renal excretion when there is an excess of calcium in the body. The normal kidney filters and reabsorbs most of the filtered calcium however, in renal disease this is reduced and blood calcium decreases. Calcium and phosphate imbalance can occur in patients with renal failure, leading to osteomalacia (defective mineralization of bone). Osteomalacia is mainly due to reduced production of 1,25-dihydroxycholecalciferol, an active form of vitamin D metabolized in the kidney. Deficiency of 1,25-dihydroxycholecalciferol reduces the absorption of calcium salts by the intestine. 

The duodenum and jejunum are capable of both absorption and secretion but absorption usually predominates. Regulation of intestinal secretion and absorption is highly complex and involves extrinsic and intrinsic neural stimuli, numerous receptor types and intercellular and intracellular transport pathways. Intracellular pathways of electrolyte transport involve membrane-associated receptors that activate cyclic nucleotide metabolism, membrane calcium channels and intracellular calcium metabolism, luminal and basal chloride channels and multiple sodium transport channels. Cholinergic stimuli tend to stimulate intestinal... 

PTH also acts to increase absorption of calcium ion by the small intestine. It does this indirectly by promoting the formation of active vitamin D in the kidney. PTH acts on the final, rate-limiting step in vitamin D synthesis, the formation of 1,25-dihydroxycholecalciferol in the kidney. If PTH is low, formation of the inactive derivative, 24,25-dihydroxycholecalciferol, is stimulated instead. Vitamin D acts on intracellular receptors in the small intestine to increase transcription of genes encoding calcium uptake systems, to up-regulate their expression. 

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