Intestinal absorption of dodecyl sulfate in the rodent: evidence
for paracellular absorption.
Amelsberg, Andree, Claudio D. Schteingart, Jurgen Stein, Wilfred J.
Simmonds, Geri A. Sawada, Norman F. H. Ho, and Alan F. Hofmann.
Division of Gastroenterology, Department of Medicine, University of
California, San Diego, CA 92092-0813 and Drug Delivery Systems
Research Laboratory, Pharmacia and Upjohn, Inc., Kalamazoo, MI 49007,
Medicine, University of Kiel, 24105 Kiel, Germany, Division of
Gastroenterology, Department of Medicine 0813, University of
California San Diego, 9500 Gilman Drive, La Jolla CA 92093-0813,
Division of Gastroenterology, Center for Internal Medicine,
University Clinic, D-60590 Frankfurt, Germany, Department of
Physiology, University of Western Australia, Perth, Western
Australia, Drug Delivery Systems Research, Pharmacia and Upjohn,
Inc., Kalamazoo, MI., 49007, Drug Delivery Systems Research,
Pharmacia and Upjohn, Inc. Kalamazoo, MI. 49007
APStracts 3:0209G, 1996.
Experiments were performed to define the mechanism of intestinal
absorption of dodecyl sulfate, an amphipathic organic anion, whose
chemical structure resembles that of dodecanoate, a C12 fatty acid
anion. With jejunal segments perfused in single pass fashion in the
anesthetized rat, steady state absorption of dodecyl sulfate was
concentration-dependent with the apparent permeability constant
(Papp) ranging from 4 to 22 (x 10-5 cm/sec). When dodecyl sulfate
concentration was held constant and net water absorption was induced
by decreasing perfusate osmolality, dodecyl sulfate absorption
increased in direct proportion to water absorption, suggesting
absorption by solvent drag via the paracellular route. However,
dodecyl sulfate absorption continued even when water secretion was
induced by a hypertonic perfusate. Consequently for all experiments,
dodecyl sulfate absorption could be empirically described as the sum
of two terms 1) absorption in the absence of water absorption (Papp =
5.6 (x 10-5 cm/sec.) and 2) absorption induced by water movement
[([delta]Papp/[delta]water absorption = 0.2 (x 10-5 cm/sec) / [mu]l
segment-1 min-1]. In a polarized epithelial monolayer of renal
epithelial cells (MDCK), dodecyl sulfate was absorbed predominantly
by a paracellular pathway, as the absorption rate increased threefold
when paracellular junction pore size was increased by the addition of
cytochalasin D. The calculated apparent radius was 2.9 [angstrom]a,
indicating that the cross section of the molecule, not its length,
determined the rate of absorption. It is concluded that absorption of
dodecyl sulfate in the intact animal occurs slowly and mostly via the
paracellular route because the fixed negative charge on the molecule
retards rapid passive entry into the enterocyte as occurs with
protonated fatty acids. Absorption of dodecyl sulfate persisting
despite net water secretion suggests that a low level of
transcellular absorption across the jejunal enterocyte also occurs
Received 22 April 1994; accepted in final form 14 September 1996.
APS Manuscript Number G143-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996