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Department A, Panum Institute, University of Copenhagen, Denmark.

1. The effect on ionic permeability of frog brain endothelium of various second messengers was studied by a technique based on continuous recording of the electrical resistance of the venular endothelium in vivo. 2. Augmentation of the cytosolic Ca2+ concentration in endothelial cells induced with the ionophores ETH 1001 and A23187 increased ion permeability significantly as reflected in the reduced electrical resistance. 3. The electrical resistance fell reversibly within 1-2 s after administration of Ca2+-activating agents. The maximal effect was a reduction to about 0.70 times the pre-experimental resistance value. The resistance decrease was similar to that induced by several inflammatory mediators (Olesen & Crone, 1986). 4. Administration of the following agents did not change the electrical wall resistance: 8-bromo-cyclic AMP, dibutyryl-cyclic AMP, forskolin, 8-bromo-cyclic GMP, dibutyryl-cyclic GMP, sodium nitroprusside, phorbol myristate acetate (a protein kinase C stimulator). Changes in cytosolic Mg2+ did not affect permeability. 5. Ca2+ may be an important cytosolic signal in the endothelial cell, acting as an intracellular mediator for several permeability-augmenting substances.