DIFFUSION OF NONELECTROLYTES IN THE CANINE TRACHEA - EFFECT OF TIGHT JUNCTION

We recently demonstrated through theoretical modeling that the exhaled ethanol (EtOH) profile from humans is consistent with a molecular dif fusion coefficient (cm(2)/s) in the bronchial mucosa (D-ti) that is on ly 8% of the diffusion coefficient in water (D-w; J. Appl. Physiol. 75 : 2439-2449, 1993). Because of the small oil-water partition coefficie nt (lambda(o:w)) of EtOH (h lambda(o:w) = 0.074), the reduced diffusio n coefficient may be due, in part, to the epithelial tight junction in the paracellular pathway. We hypothesized that opening the tight junc tion would open an aqueous pathway and increase the diffusion coeffici ent of small (mel wt <100) hydrophilic compounds. We mounted the mucos a from the membranous canine trachea in an Ussing-type diffusion cell and measured the diffusion coefficient of 2-ethoxyethanol (2-Ethx; lam bda(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 Ca2 and Mg2+ with 0.5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N ',N'-tetraacetic acid, and its integrity was assessed by measuring the transepithelial electrical resistance. D-ti/D-w in the presence of Ca 2+ and Mg2+ was 0.39, 0.34, and 0.39 for 2-Ethx, EtOH, and MEK, respec tively, and increased 24.6, 11.7, and 1.11% in the absence of Ca2+ and Mg2+. We conclude that the effect of the tight junction on D-ti incre ases with increasing water solubility but can account for only a small portion of the reduced D-ti of EtOH as predicted by exhaled profiles.