title: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Japan.
authors.forename: Kin-Ya
authors.initials: KY
authors.lastname: Ohta
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Inoue
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yuasa
mesh_terms: D000465:Algorithms; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002352:Carrier Proteins; D005990:Glycerol