NEW ASPECTS OF MECHANISMS AND REGULATION OF INTESTINAL CALCIUM-TRANSPORT

Only in the duodenum and in the colon calcium is absorbed by a cellula r 1,25alpha-Vitamin D3-dependent transport, mechanism. Calcium absorpt ion is highest in the proximal large intestine, about ten times higher than in the duodenum or in the descending colon. 1,25alpha-Vitamin D3 stimulates calcium transport by genomic (slow effect: synthesis of cy tosolic calcium binding protein CabP and basolateral Ca-ATPase) and no n-genomic action (rapid effect: transcaltachia, liponomic effect at th e brush border membrane). CabP-dependent translocation across the cyto sol is thought to be rate limiting step of cellular calcium transport. However, only about 50% of calcium absorption is cellular mediated bu t the same amount of calcium convectively is absorbed by transepitheli al water flow across the paracellular pathway (solvent drag effect). 1 ,25alpha-Vitamin D3 not only activates cellular calcium absorption but also increases paracellular permeability for calcium by an unknown me chanism. However, essential steps in the cascade from the interaction of 1,25alpha-Vitamin D3 with the specific receptor over the regulation of the synthesis of calcium binding and transporting proteins to the induction of cellular calcium transport are not as yet clearly underst ood. The exact feedback mechanism of synchronized calcium transport ac ross the distinct subcellular compartiments seems also to be resolved. Cellular calcium transport is not found in the jejunum or in the ileu m, what can be explained by the absence of specific 1,25alpha-Vitamin D3-dependent carrier systems in these segments. On the other hand calc ium is secreted across the jejunum and ileum by an anomalous solvent d rag effect. Hence, intestinal calcium metabolism seems to underline an eneteroenteral circuit: 1,25alpha-Vitamin D3-controlled cellular calc ium absorption across the duodenum is followed by paracellular calcium secretion across the jejunum and ileum. The carrier in the proximal c olon which works at the optimal level already under normal nutritional condition could be of physiological importance for the reclamation of unabsorbed dietary calcium and for the reabsorption of calcium that i s secreted across the distal small intestine. Under certain pathophysi ological conditions, i.e. malabsorption in proximal segments or malnut rition, calcium in addition may be conserved by the 1,25alpha-Vitamin D3-sensitive carrier in the descending colon. Possibly the segmental h eterogeneity of cellular and paracellular calcium transport across the small and large intestine may be of physiological importance in the o verall coordination between intestinal calcium metabolism and vitamin D3-parathyroid hormon feedback mechanism.