Carrier-Mediated Transport of Glycerol in the Perfused Rat Small Intestine

Abstract

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 study 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. In situ single-pass perfusion was conducted using a 10-cm midgut segment of the male Wistar rat, and the absorption of [3H]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/cm2 and the Michaelis constant (K(m)) was 1.04 mM, giving a J(max)/K(m) of 7.39 x 10(-5) cm/s. The membrane permeability coefficient for passive transport (P(m,d)) was 6.89 x 10(-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.