Trans‐ and paracellular calcium transport across the colonic mucosa after short‐ and long‐term treatment with 1,25‐dihydroxyvitamin D3

Abstract

The electrical parameters and the unidirectional fluxes of 45Ca and 3H-mannitol were measured in preparations of rat colon descendens freed from the muscularis externa and mounted in a modified Ussing-chamber. Two criteria were used to differentiate between changes in the trans- and the paracellular calcium transport after treatment with 1,25 (OH)2D3: (a) the fluxes of the simultaneously measured 3H-mannitol as a paracellular marker; (b) the 45Ca fluxes in preparations with clamped potentials. After a short-time (6 h) pretreatment by s.c. administration of 1,25 (OH)2D3 (250 ng kg-1) in normal rats the mucosa (m) to serosa (s) 45Ca flux under short circuit conditions increased about 65%, whereas the electrical parameters and the 3H-mannitol fluxes remained unchanged. In clamped epithelia the PD-independent m to s 45Ca flux was increased, whereas the PD-dependent flux remained unchanged. In contrast, after long-time (4 days) induction by 1,25(OH)2D3 (a) the m to s 45Ca flux increased under short circuit conditions by about 100% and the m to s 3H-mannitol flux increased by 50%, (b) PD and Isc decreased by more than 60%, whereas tissue resistance was the same, (c) in clamped epithelia the calculated PD-independent, transcellular m to s 45Ca flux was 2.4 times and the PD-dependent, paracellular 45Ca-flux was 1.9 times higher than in controls, whereas the s to m 45Ca flux remained unchanged. On the basis of the relevant references the following conclusions were drawn: (a) after short-time exposure to 1,25(OH)2D3 only the PD-dependent, transcellular m to s calcium transport is increased; this is probably due to a liponomic effect of 1,25(OH)2D3 at the brush border membrane. (b) After long-time induction the PD-dependent, paracellular m to s transport of calcium and mannitol is increased additionally. It is hypothesized that a solvent drag effect might be responsible for the increased paracellular calcium flux after long-time treatment with 1,25(OH)2D3. It is concluded that long-term treatment with 1,25(OH)2D3 stimulates paracellular m to s movement of other solutes than that of calcium.