AJP - Gastrointestinal and Liver Physiology, Vol 255, Issue 4 454-G461, Copyright © 1988 by American Physiological Society
Hormonal regulation of hepatocyte tight junctional permeability
P. J. Lowe, K. Miyai, J. H. Steinbach and W. G. Hardison
Department of Medicine, Veterans Administration Medical Center, San Diego, California.
We have investigated the effects of hormones on the permeability of the
hepatocyte tight junction to two probes, [14C]sucrose and horseradish
peroxidase, using one-pass perfused rat livers. Using a single injection of
horseradish peroxidase we have demonstrated that this probe can enter bile
by two pathways that are kinetically distinct, a fast pathway, which
corresponds to the passage of the probe through the hepatocyte tight
junctions, and a slow pathway, which corresponds to the transcytotic entry
into bile. The passage of horseradish peroxidase through the hepatocyte
tight junctions was confirmed by electron microscopic histochemistry.
Vasopressin, epinephrine, and angiotensin II, hormones that act in the
hepatocyte through the intracellular mediators calcium, the inositol
polyphosphates, and diacylglycerol, increased the bile-to-perfusion fluid
ratio of [14C]sucrose and the rapid entry of horseradish peroxidase into
bile, indicating that the permeability of the tight junctions to these
probes was increased. The effect of these hormones was dose dependent and
in the cases of angiotensin II and epinephrine was inhibited by the
specific inhibitors [Sar1, Thr8]angiotensin II and prazosin, respectively.
Dibutyryl adenosine 3',5'-cyclic monophosphate did not affect the
[14C]sucrose bile-to-perfusion fluid ratio or the fast entry of horseradish
peroxidase into bile. These results suggest that the hepatocyte tight
junction can no longer be considered a static system of pores separating
blood from bile. It is rather a dynamic barrier potentially capable of
influencing the composition of the bile.
