Diffusion of non-electrolytes in the canine trachea: effect of
tight junction.
George, Steven C., Albert L. Babb, Mark E. Deffebach, and Michael P.
Hlastala.
DEPARTMENTS OF CHEMICAL ENGINEERING, MEDICINE, PHYSIOLOGY AND
BIOPHYSICS, UNIVERSITY OF WASHINGTON, SEATTLE, WASHINGTON AND
DEPARTMENT OF MEDICINE, DIVISION OF PULMONARY AND CRITICAL CARE
MEDICINE, OREGON HEALTH SCIENCES UNIVERSITY AND PORTLAND VA MEDICAL
CENTER, PORTLAND, OREGON
APStracts 3:0004A, 1996.
We have recently demonstrated through theoretical modeling that the
exhaled ethanol (EtOH) profile from humans is consistent with a
molecular diffusion coefficient (cm2.s-1) in the bronchial mucosa,
Dt, that is only 8% of the diffusion coefficient in water, Dw
(George, et al., J. Appl. Physiol. 75(6):2439-2449, 1993). Due to the
small oil:water partition coefficient, [lambda]o:w, of EtOH
([lambda]o:w=0.074), the reduced diffusion coefficient may be due, in
part, to the epithelial tight junction in the paracellular pathway.
We hypothesized that opening the tight junction would open an aqueous
pathway and increase the diffusion coefficient of small (MW<100)
hydrophilic compounds. We mounted the mucosa from the membranous
canine trachea in an Ussing-type diffusion cell and measured the
diffusion coefficient of 2-ethoxyethanol (2-Ethx, [lambda]o:w=0.042),
EtOH, and methyl ethyl ketone (MEK, [lambda]o:w=1.04) in the presence
and absence of the epithelial tight junction. The tight junction was
opened using a phosphate buffered saline free of Ca++ and Mg++ with
0.5 mM EGTA, and it's integrity assessed by measuring the
transepithelial electrical resistance. The ratio Dt:Dw in the
presence of Ca++ and Mg++ was 0.39, 0.34, and 0.39 for 2-Ethx, EtOH,
and MEK, respectively, and increased 24.6%, 11.7%, and 1.11% in the
absence of Ca++ and Mg++. We conclude that the effect of the tight
junction on Dt increases with increasing water solubility, but can
account for only a small portion of the reduced Dt of EtOH as
predicted by exhaled profiles.
Received 27 July 1995; accepted in final form 6 December 1995.
APS Manuscript Number A825-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96