U. Fagerholm et al., Jejunal permeability in humans in vivo and rats in situ: investigation of molecular size selectivity and solvent drag, ACT PHYSL S, 165(3), 1999, pp. 315-324
The mechanisms controlling rates and routes for intestinal absorption of nu
trients and small compounds are still not fully clarified. In the present s
tudy we aimed to investigate the effect of solvent drag on intestinal perme
ability of compounds with different molecular sizes in humans and rats. The
effective intestinal permeabilities (P-eff) of hydrophilic compounds (MW 6
0-4000) were determined in the single-pass perfused jejunum in humans in vi
vo and rats in situ under iso- and hypotonic conditions. The transport mech
anism(s) of water and the importance of the solvent drag effect were invest
igated by the use of D2O. This is the first report in humans establishing t
he relation between in vivo measured jejunal P-eff and molecular size for h
ydrophilic compounds. In addition, in rats we also found a molecular-size s
electivity for hydrophilic compounds similar to man. The jejunal P-eff of w
ater and urea (MW 60) in both species were several times higher than predic
ted from their physicochemical properties. In humans, the jejunal absorptio
n of urea and creatinine (MW 113) was increased by solvent drag, while no e
ffect was found for the other investigated compounds. In rats. P-eff for ur
ea and creatinine were unaffected. In conclusion, it is still unclear ii so
lvent drag occurs mainly through the para- or transcellular route, although
, results from this study further add to our earlier reports suggesting tha
t the transcellular route is most important from a quantitative point of vi
ew regardless of physicochemical properties of the transported compounds.