Regulation of ion permeability in frog brain venules. Significance of calcium, cyclic nucleotides and protein kinase C.

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.