Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat

Abstract

The lumen of the small intestine in anesthetized rats was recirculated with 50 ml perfusion fluid containing normal salts, 25 mM glucose and low concentrations of hydrophilic solutes ranging in size from creatinine (mol wt 113) to Inulin (mol wt 5500). Ferrocyanide, a nontoxic, quadrupally charged anion was not absorbed; it could therefore be used as an osmotically active solute with reflection coefficient of 1.0 to adjust rates of fluid absorption, Jv, and to measure the coefficient of osmotic flow, Lp. The clearances from the perfusion fluid of all other test solutes were approximately proportional to Jv. From Lp and rates of clearances as a function of Jv and molecular size we estimate (a) the fraction of fluid absorption which passes paracellularly (approx. 50%), (b) coefficients of solvent drag of various solutes within intercellular junctions, (c) the equivalent pore radius of intercellular junctions (50 A) and their cross sectional area per unit path length (4.3 cm per cm length of intestine). Glucose absorption also varied as a function of Jv. From this relationship and the clearances of inert markers we calculate the rate of active transport of glucose, the amount of glucose carried paracellularly by solvent drag or back-diffusion at any given Jv and luminal glucose concentration and the concentration of glucose in the absorbate. The results indicate that solvent drag through paracellular channels is the principal route for intestinal transport of glucose or amino acids at physiological rates of fluid absorption and concentration. In the absence of luminal glucose the rate of fluid absorption and the clearances of all inert hydrophilic solutes were greatly reduced. It is proposed that Na-coupled transport of organic solutes from lumen to intercellular spaces provides the principal osmotic force for fluid absorption and triggers widening of intercellular junctions, thus promoting bulk absorption of nutrients by solvent drag. Further evidence for regulation of channel width is provided in accompanying papers on changes in electrical impedance and ultrastructure of junctions during Na-coupled solute transport.

The effect of L‐leucine on the absorption of levodopa, studied by regional jejunal perfusion in man.

“…This hypothesis has support in the fact that levodopa is a small and hydrophilic molecule and that the jejunal epithelia is more leaky than the tight epithelium of the rectum, where no absorption of levodopa has been demonstrated (Eisler et al, 1981;Schultz, 1981). In general, nutrients such as amino acids and D-glc alone or in combination with hypoosmolarity, increase the absorption of compounds by solvent drag and/or paracellular diffusion (Pappenheimer & Reiss, 1987;Winne, 1974). Amino acids may therefore, have a dual effect on the intestinal absorption of levodopa.…”

“…L-leucine (L-leu) was investigated as a competing amino acid with antipyrine, benserazide and D-glucose (D-glc) as controls. The fluid flux across the jejunal membrane and the osmolality of the intestinal perfusate were also investigated, since it is possible that the presence of nutrients and differences in osmotic pressure could influence drug absorption (Pappenheimer & Reiss, 1987;Winne, 1974 (Kerlin et al, 1982;Soergel, 1971). The subjects were recumbent during the perfusion period of 200 min.…”

Factors affecting intestinal starch digestion in ruminants: A review

“…A mechanism of absorption has been proposed whereby sugars exit the lumen via the intercellular spaces, a process termed solvent drag (Madara and Pappenheimer 1987;Pappenheimer and Reiss 1987;Pappenheimer 1990). For this process to occur, luminal glucose must be present at high concentrations (>25 mM), and concentrations must exceed approximately 200 mM before paracellular absorption would exceed active transport (Pappenheimer and Reiss 1987), which may not occur under physiological conditions (Ferraris et al 1990). These processes may indeed contribute in experiments where glucose is infused postruminally (Kreikemeier et al 1991;Kreikemeier and Harmon 1995).…”

Development of therapeutic proteins: advances and challenges

“…The paracellular transport mechanism is proteolytic deficient, engages with intercellular water channels, and is considered a suitable pathway for the transportation of hydrophilic small molecules like proteins (Pappenheimer and Reiss, 1987;Salamat-Miller and Johnston, 2005). However, most of the proteins have a large molecular weight and may exhibit low bioavailability, especially following oral administration because of the tight junctions between the epithelial cells.…”