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 perfused with a gelatin-containing physiological salt solution in vitro. Various phorbol-related compounds that are known to have different affinities 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-dibutyrate (PDB), 12-deoxyphorbol 13-phenylacetate (DOPPA), thymeleatoxin (TMX), and resiniferatoxin (RFX), each at a concentration of 1 microM, were found to increase permeability. Pretreatment with the PKC inhibitor Ro 31-8220 (1 microM) significantly reduced the response to all of these compounds. Indomethacin (1 microM), on the other hand, reduced only the effect of RFX. 12-Deoxyphorbol 13-phenylacetate 20-acetate (DOPPAA) (1 microM) and BK (10 microM) did not increase CC leakage. These results suggest that the Ca(2+)-dependent PKC alpha-isoenzyme was involved in the increase in endothelial permeability. BK does not appear to stimulate PKC activity in this experimental situation.
Department of Pharmacy, School of Applied Sciences, De Montfort University, Leicester, U.K.
A M
AM
Northover
B J
BJ
Northover
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D002244:Carbon / Q000493:pharmacokinetics*; D003102:Colloids; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000098:blood supply; D007527:Isoenzymes / Q000819:agonists / Q000502:physiology*; D008643:Mesentery / Q000098:blood supply; D010703:Phorbol Esters / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D011493:Protein Kinase C / Q000819:agonists / Q000502:physiology*; D051571:Protein Kinase C-alpha; D051381:Rats
D003102:Colloids; D016861:Cyclooxygenase Inhibitors; D004224:Diterpenes; D007211:Indoles; D007527:Isoenzymes; D010703:Phorbol Esters; D011453:Prostaglandins; D002244:Carbon; C080287:thymeleatoxin; C024353:resiniferatoxin; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D001920:Bradykinin; C064758:Ro 31-8220; D007213:Indomethacin