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.
Northover
A M
AM
Department of Pharmacy, School of Applied Sciences, De Montfort University, Leicester, U.K.
Northover
B J
BJ
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