We examined ZO-1 protein content in cultured retinal vascular endothel
ial cells to test the hypothesis that histamine alters tight-junction-
protein expression. Histamine (10(-8)-10(-4) M) causes a reversible co
ncentration-dependent reduction of ZO-1 protein content, mediated by b
oth H-1 and H-2 receptors. Histamine reduces ZO-1 expression within th
e time associated with increased paracellular permeability. Tight-junc
tion-protein alterations may be a novel explanation for the mechanism
by which vasoactive agents increase microvascular permeability.