Carrier-mediated transport of glycerol in the perfused rat small intestine

Studies using the closed loop and everted sacs of the rat small intestine recently prompted us to suggest that carrier-mediated transport is involved in the intestinal absorption of glycerol. Although it could be mediated by a novel carrier system, little information is available. The aim of the present stud), was to kinetically characterize carrier-mediated glycerol transport in the perfused rat small intestine to help in identifying the carrier involved and to explore the possibility that the carrier might be used as a pathway for oral drug delivery and a target for drug development. lit situ single-pass perfusion was conducted using a 10-cm midgut segment of the male Wistar rat, and the absorption of [H-3] glycerol was evaluated by its disappearance from the intestinal lumen. The absorption of glycerol was saturable and significantly reduced by removing Na+ from the perfusion solution, suggesting the involvement of a Na+-dependent carrier-mediated transport system. The concentration-dependent absorption profile was successfully analyzed by assuming Michaelis-Menten type carrier-mediated transport and simultaneous passive (diffusive) transport. The maximum transport rate (J(max)) was 77.0 pmol/s/cm(2) and the Michaelis constant (K-m) was 1.04 m(M), giving a J(max/)K(m) of 7.39 X 10(-5) cm/s. The membrane permeability coefficient for passive transport (P-m,P-d) was 6.89X10(-5)cm/s, slightly smaller than J(max)/K-m. Therefore, it could be the major mechanism of intestinal glycerol absorption in the low concentration range where carrier-mediated transport conforms to linear kinetics represented by J(max)/K-m. Furthermore, carrier-mediated glycerol transport was found to be inhibited by glycerol 3-phosphate, monoacetin and diglycerol, indicating that the carrier system may be shared by these structural analogues. Thus, the present study has successfully demonstrated and characterized carrier-mediated glycerol transport in the perfused rat small intestine which is a physiologically relevant model.