Involvement of protein kinase C in the control of microvascular permeability to colloidal carbon.
The vasculature of the rat small intestine and attached mesentery was perfused in vitro with a gelatin-containing physiological salt solution (GPSS). The inclusion of colloidal carbon (CC) in the perfusate towards the end of the experimental period enabled the "leakiness" of microvessels in the villi to be determined, since "leaky" vessels trap CC in their walls. Addition to the perfusate of the inflammatory agonists platelet-activating factor (PAF, 5 x 10(-6) M) or 5-hydroxytryptamine (5-HT, 1 x 10(-4) M), or the microtubule-disrupting agents podophyllotoxin (5 x 10(-5) M), or colcemid (5 x 10(-5) M), or the protein kinase C (PKC) activator phorbol 12, 13-dibutyrate (PDB, 1 x 10(-6) M), caused significantly increased microvascular "blackening" as assessed by image analysis. 4 alpha-phorbol 12, 13-didecanoate (PDD, 1 x 10(-6) M) had no effect. Pretreatment with the PKC inhibitor Ro 31-8220 [corrected] (1 x 10(-6) M) significantly reduced the effects of PAF, 5-HT and PDB, but not those of podophyllotoxin or colcemid. These results suggest, therefore, that PKC is involved in the permeability-enhancing effects of PAF, 5-HT and PDB. Pretreatment with indomethacin (1 x 10(-6) M) as a cyclooxygenase inhibitor did not reduce the response to PDB, indicating that prostaglandin release is of minor importance in the PDB-induced increase in microvascular permeability.
Northover
A M
AM
Department of Pharmacy, School of Applied Sciences, De Montfort University, Leicester, UK.
Northover
B J
BJ
D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D002244:Carbon; D003102:Colloids; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D003102:Colloids; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D010972:Platelet Activating Factor; D012702:Serotonin Antagonists; D012701:Serotonin; D002244:Carbon; D011493:Protein Kinase C; C064758:Ro 31-8220; D007213:Indomethacin