Involvement of nitric oxide in permeability alteration and F-actin redistribution induced by phorbol myristate acetate in endothelial cells.
We have previously reported that phorbol myristate acetate (PMA) caused a decrease in endothelial permeability during the first 1 to 1.5 h of exposure and thereafter an increase for up to 6 h. This permeability alteration was correlated with a time-dependent redistribution of F-actin, i.e., an increase in dense peripheral bands was observed during the first hour of PMA incubation and a disruption of the bands after 6 h. In the present study, we found that this PMA-induced alteration of permeability is L-arginine dependent, since the low permeability prevailed for up to 6 h when extracellular L-arginine was available. Moreover, we noted that administration of N-nitro-L-arginine methylester (L-NAME) to PMA-treated cells caused a direct increase in permeability. The redistribution of F-actin induced by PMA was also L-arginine dependent, since the number of dense peripheral bands continued to increase for up to 6 h when extracellular L-arginine was available, and these bands were directly disrupted when L-NAME was added. These results suggest that the tight contact between PMA-treated endothelial cells is maintained by a redistribution of F-actin elicited by the endogenous production of nitric oxide.
D000199:Actins / Q000187:drug effects*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D000199:Actins; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D013755:Tetradecanoylphorbol Acetate; D019331:NG-Nitroarginine Methyl Ester