Prednisolone-induced Ca2+ malabsorption is caused by diminished expression of the epithelial Ca2+ channel TRPV6

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2007-01, Vol.292 (1), p.G92-G97
• Main Authors: Huybers, Sylvie, Naber, Ton H J, Bindels, René J M, Hoenderop, Joost G J
• Format: Article
• Language: English
• Subjects: Animals; Calbindins; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - genetics; Calcium Radioisotopes; Disease Models, Animal; Duodenum - physiology; Duodenum - physiopathology; Gene Expression Regulation - drug effects; Intestinal Absorption; Intestinal Mucosa - physiology; Intestinal Mucosa - physiopathology; Malabsorption Syndromes - physiopathology; Mice; Mice, Inbred C57BL; Polymerase Chain Reaction; Prednisolone - pharmacology; S100 Calcium Binding Protein G - genetics; TRPV Cation Channels - drug effects; TRPV Cation Channels - genetics
• ISSN: 0193-1857
• DOI: 10.1152/ajpgi.00317.2006

Glucocorticoids, such as prednisolone, are often used in clinic because of their anti-inflammatory and immunosuppressive properties. However, glucocorticoids reduce bone mineral density (BMD) as a side effect. Malabsorption of Ca2+ in the intestine is supposed to play an important role in the etiology of low BMD. To elucidate the mechanism of glucocorticoid-induced Ca2+ malabsorption, the present study investigated the effect of prednisolone on the expression and activity of proteins responsible for active intestinal Ca2+ absorption including the epithelial Ca2+ channel TRPV6, calbindin-D(9K), and the plasma membrane ATPase PMCA1b. Therefore, C57BL/6 mice received 10 mg/kg body wt prednisolone daily by oral gavage for 7 days and were compared with control mice receiving vehicle only. An in vivo 45Ca2+ absorption assay indicated that intestinal Ca2+ absorption was diminished after prednisolone treatment. We showed decreased duodenal TRPV6 and calbindin-D(9K) mRNA and protein abundance in prednisolone-treated compared with control mice, whereas PMCA1b mRNA levels were not altered. Importantly, detailed expression studies demonstrated that in mice these Ca2+ transport proteins are predominantly localized in the first 2 cm of the duodenum. Furthermore, serum Ca2+ and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] concentrations remained unchanged by prednisolone treatment. In conclusion, these data suggest that prednisolone reduces the intestinal Ca2+ absorption capacity through diminished duodenal expression of the active Ca2+ transporters TRPV6 and calbindin-D(9K) independent of systemic 1,25(OH)2D3.