Differential effects of inhibitors of cellular function on inflammatory mediator-stimulated increases in vascular permeability.
The suffused noneverted cheek pouch of pentobarbital anesthetized hamsters was used to study the effects of various inhibitors of receptor/cellular function on inflammatory mediator stimulated increases in vascular permeability. Fluorescein isothiocynate dextran (FITC-D, 70,000 Da) was utilized as a tracer, and intra-vital light microscopy was employed to monitor the formation of vascular leakage sites while direct measurement of plasma and suffusate tracer concentrations were used to monitor tracer clearance. Vascular permeability increases were triggered by suffusing the cheek pouch with histamine, bradykinin, or Compound 48/80 which stimulated the formation of focal FITC-D leakage sites in the postcapillary venules resulting in marked increases in [FITC-D]S, [FITC-D]S/[FITC-D]p. 10(-6), and FITC-D clearance. Saline, calmidazolium, and papaverine lacked intrinsic permeability increasing activity, and failed to alter histamine, bradykinin, and compound 48/80 stimulated formation of venular FITC-D leakage sites and increases in [FITC-D]S, [FITC-D]S/[FITC-D]p. 10(-6), and FITC-D clearance. In contrast, treatment with cytochalasin B, DDAVP, diphenhydramine, tubulazole C, or verapamil inhibited histamine and Compound 48/80 stimulated formation of venular FITC-D leakage sites and increases in [FITC-D]S, [FITC-D]S/[FITC-D]p. 10(-6), and FITC-D clearance. Bradykinin stimulated formation of venular FITC-D leakage sites and increases in [FITC-D]S, [FITC-D]S/[FITC-D]p. 10(-6), and FITC-D clearance were not affected by treatment with calmidazolium, cytochalasin B, DDAVP, diphenhydramine, tubulazole C, or verapamil. These findings demonstrate that inflammatory mediator stimulated increases in vascular permeability may be differentially affected by inhibitors of receptor/cellular function.
Grega
G J
GJ
Department of Pharmacology, University of Houston, Science & Research II, Texas 77204-5515.
Adamski
S W
SW
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D006224:Cricetinae; D003911:Dextrans / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics / Q000031:analogs & derivatives; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D010208:Papaverine / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D003911:Dextrans; D006633:Histamine Antagonists; D011956:Receptors, Cell Surface; C015219:fluorescein isothiocyanate dextran; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D010208:Papaverine; D016650:Fluorescein-5-isothiocyanate; D001920:Bradykinin