Paracellular phosphate absorption in rat colon: a mechanism for enema-induced hyperphosphatemia.
The mechanism of colonic phosphate absorption is not well defined. We measured unidirectional phosphate fluxes across rat distal colon epithelium in the absence of transepithelial electrochemical gradients. Steady-state mucosal-to-serosal flux (Jms) was not different from the serosal-to-mucosal flux (Jsm), generating no net flux (Jnet = Jms - Jsm, was not different from "0'). Simultaneous fluxes of mannitol, a paracellular probe, exhibited an identical flux pattern, suggesting that phosphate flux across the colonic epithelium may be mediated through the paracellular pathway. Tight junction permeability was increased with mucosal addition of taurodeoxycholate (TDC, 2 mM) which caused a prompt increase in transepithelial conductance from 7.03 +/- 0.35 to 13.88 +/- 0.35 mS/cm2 (p < 0.001). This was associated with an increase in Jsm, but no change in Jms, for mannitol, resulting in a net flux in the secretary direction. Identical TDC-induced changes were observed in phosphate fluxes, again suggesting phosphate permeation through the intercellular, mannitol pathway. A significant correlation was observed between the permeability of phosphate and the permeability of mannitol, measured both in the mucosal-to-serosal and the serosal-to-mucosal directions and under both control and experimental (mucosal TDC) conditions. Thus, colonic phosphate transport is mediated through the paracellular pathway and enema with high phosphate concentrations (1,760 times blood concentration), can trigger rapid and massive phosphate absorption through this diffusive pathway.
Hu
M S
MS
Medical and Research Services, Veterans Health Administration Medical Center, Sepulveda, Calif., USA.
Kayne
L H
LH
Jamgotchian
N
N
Ward
H J
HJ
Lee
D B
DB
D000818:Animals; D003106:Colon / Q000378:metabolism*; D004733:Enema / Q000009:adverse effects*; D007408:Intestinal Absorption; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D010539:Permeability; D010710:Phosphates / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013657:Taurodeoxycholic Acid / Q000494:pharmacology; D019108:Tight Junctions / Q000378:metabolism
D010710:Phosphates; D008353:Mannitol; D013657:Taurodeoxycholic Acid