title: Molecular and transport effects of 1,25-dihydroxyvitamin D3 in rat duodenum.
abstract: The saturable component of transmural calcium transport in rat duodenum is transcellular, dependent on vitamin D, and can be evaluated by in situ gut loops or everted sacs. Vitamin D action at the molecular level can be studied by analyzing the response in terms of calcium-binding protein (CaBP; Mr congruent to 9000) biosynthesis to exogenous 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3). In vitamin D-replete animals, the CaBP response occurs within 1 h of intraperitoneal injection when the animals have been fed a high-calcium diet (III), but in 7 h if the animals have been fed a low-calcium diet(I). The latter response appears to be transcriptional, whereas the former seems posttranscriptional. In vitamin D-deficient animals, exogenous 1,25-(OH)2-D3 evokes a CaBP response that occurs 7-8 h after treatment and is transcriptional in nature. Calcium uptake by isolated duodenal cells can be stimulated by prior in vivo treatment with 1,25-(OH)2-D3. Peak response times parallel those found with CaBP biosynthesis, i.e., 3 h in cells from vitamin D-replete animals fed diet III, 7 h in cells from vitamin D-replete animals fed diet I, and 12 h in cells from vitamin D-deficient animal. Cycloheximide treatment appears to inhibit these responses. Moreover, everted sacs from vitamin D-replete animals fed diets III and I show an early and a delayed transport response, respectively. Studies with brush border membrane vesicles prepared from rat duodenum have shown calcium uptake to be vitamin D-dependent. Part of this uptake involves binding to the inner aspect of the membrane and may involve a high-affinity CaBP. Thus a major component of the action of vitamin D in stimulating calcium transport appears to involve protein synthesis. The time and molecular nature of these responses depend on the calcium intake and vitamin D status of the animals. A model of calcium movement through the intestinal cell is included.
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002117:Calcitriol / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis; D014808:Vitamin D Deficiency / Q000378:metabolism
chemical_list: D064030:S100 Calcium Binding Protein G; D003513:Cycloheximide; D002117:Calcitriol; D002118:Calcium