TITLE:
Nonlinear Intestinal Absorption of Fluorescein Isothiocyanate Dextran 4, 000 Caused by Absorptive and Secretory Transporting System
AUTHORS:
Mikio Tomita, Rie Ohkubo, Shohei Ouchi, Chise Kawahata, Masahiro Hayashi
KEYWORDS:
Fluorescein Isothiocyanate Dextran 4, 000, Nonlinear Absorptive Transport, Nonlinear Secretory Transport, Rat Ileal Intestine
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.2 No.3,
July
28,
2011
ABSTRACT: The mechanism of the nonlinear concentration dependence of the intestinal absorption of fluorescein isothiocyanate dextran 4,000 (FD-4) was studied using in situ rat intestinal loops and the in vitro Ussing-type chamber method. The intestinal absorption rate constant of FD-4, as evaluated by the intestinal loop method, increased significantly in a nonlinear fashion as the FD-4 concentration increased up to 0.2 mM and tended to decrease at concentrations higher than 0.2 mM. The mucosal-to-serosal permeation of FD-4 across rat ileal sheets, as evaluated by the in vitro Ussing-type chamber method, also increased in a nonlinear fashion in the low concentration range (0.01 - 0.02 mM), before decreasing as the concentration increased further, whereas serosal-to-mucosal permeation decreased in a concentration-dependent manner. In addition, mucosal-to-serosal flux and serosal-to-mucosal flux were increased and reduced in the presence of the metabolic inhibitor 2, 4-dinitrophenol, respectively. These results suggest that FD-4 is predominantly secreted into the intestinal lumen by an efflux transport system.