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Dept. of Human Physiology, School of Medicine, University of California at Davis, Davis, California 95616
We previously proposed a two-pathway model for
solute and water transport across vascular endothelium (Fu, B. M., R. Tsay, F. E. Curry, and S. Weinbaum. J. Biomech.
Eng. 116: 502-513, 1994) that hypothesized the
existence of a continuous slit 2 nm wide along tight junction strands
within the interendothelial cleft in parallel with 20 × 150-nm
breaks in tight junctions. We tested this model by measuring capillary
permeability coefficients (P) to a
small solute (sodium fluorescein, radius 0.45 nm), assumed to permeate
primarily the 2-nm small pore, and an intermediate-sized solute
(FITC-
-lactalbumin, radius 2.01 nm) excluded from the small pore.
Mean values of the paired diffusive permeability coefficients, Psodium
fluorescein and
PFITC-
-lactalbumin,
were 34.4 and 2.9 × 10
6 cm/s, respectively,
after corrections for solvent drag and free dye
(n = 26). These permeabilities were
accounted for by transport through the large-break pathway without the
additional capacity of the hypothetical 2-nm pathway. As a further test
we examined the relative reductions of
Psodium
fluorescein and
PFITC--lactalbumin
produced by elevated intracellular cAMP. Within 20 min after the
introduction of rolipram and forskolin,
Psodium
fluorescein and
PFITC--lactalbumin
decreased to 0.67 and 0.64 times their respective baseline values. These similar responses to permeability decrease were evidence that the
two solutes were carried by a common pathway. Combined results in both
control and reduced permeability states did not support the hypothesis
that a separate pathway across tight junctions is available for solutes
with a radius as large as 0.75 nm. If such a pathway is present, then
its size must be smaller than that of sodium fluorescein.
quantitative fluorescence microscope photometry; paired measurements on single capillaries; three-dimensional junction-pore matrix model for interendothelial cleft; rolipram; forskolin
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