STIMULATION OF PROTEIN-KINASE-C ACTIVITY MAY INCREASE MICROVASCULAR PERMEABILITY TO COLLOIDAL CARBON VIA ALPHA-ISOENZYME

The vasculature of the isolated mesentery and small intestine was perf used with a gelatin-containing physiological salt solution in vitro. V arious phorbol-related compounds that are known to have different affi nities for the protein kinase C (PKC) isoenzymes, and bradykinin (BK), were tested for their ability to cause the microvascular endothelium to become permeable to injected colloidal carbon (CC). Phorbol 12,13-d ibutyrate (PDB), 12-deoxyphorbol 13-phenylacetate (DOPPA), thymelea-to xin (TMX), and resiniferatoxin (RFX), each at a concentration of 1 mu M, were found to increase permeability. Pretreatment with the PKC inhi bitor Ro 31-8220 (1 mu M) significantly reduced the response to all of these compounds. Indomethacin (1 mu M), on the other hand, reduced on ly the effect of RFX. 12-Deoxyphorbol 13-phenylacetate 20-acetate (DOP PAA) (1 mu M) and BK (10 mu M) did not increase CC leakage. These resu lts suggest that the Ca2+-dependent PKC alpha-isoenzyme was involved i n the increase in endothelial permeability. BK does not appear to stim ulate PKC activity in this experimental situation.