Bradykinin- and substance P-induced edema formation in the hamster cheek pouch is tyrosine kinase dependent.
The purpose of this study was to determine whether protein tyrosine kinase, a ubiquitous family of intracellular signaling enzymes that regulates endothelial cell function, modulates bradykinin- and substance P-induced increase in macromolecular efflux from the intact hamster cheek pouch microcirculation. Using intravital microscopy, I found that suffusion of bradykinin or substance P (each, 0.5 and 1.0 microM) onto the cheek pouch elicited significant, concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-dextran (FITC-dextran; molecular mass, 70 kDa; P < 0.05). These responses were significantly attenuated by suffusion of genistein (1.0 microM) or tyrphostin 25 (10 microM), two structurally unrelated, nonspecific protein tyrosine kinase inhibitors (P < 0.05). Conceivably, the kinase(s) involved in this process could be agonist specific because genistein was more effective than tyrphostin 25 in attenuating bradykinin-induced responses while the opposite was observed with substance P. Both inhibitors had no significant effects on adenosine (0.5 M)-induced responses (P > 0.5). Collectively, these data suggest that the protein tyrosine kinase metabolic pathway modulates, in part, the edemagenic effects of bradykinin and substance P in the intact hamster cheek pouch microcirculation in a specific fashion.
Rubinstein
Israel
I
Department of Medicine, Colleges of Medicine and Pharmacy, University of Illinois at Chicago, and Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612-4325, USA. IRubinst@uic.edu
D000818:Animals; D001920:Bradykinin / Q000009:adverse effects / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002610:Cheek / Q000098:blood supply*; D006224:Cricetinae; D003911:Dextrans / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000378:metabolism / Q000503:physiopathology; D018715:Microscopy, Video; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000009:adverse effects / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
D003911:Dextrans; D047428:Protein Kinase Inhibitors; D020032:Tyrphostins; C015219:fluorescein isothiocyanate dextran; C079836:tyrphostin 25; D013373:Substance P; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D016650:Fluorescein-5-isothiocyanate; D001920:Bradykinin