Platelet-activating factor stimulates protein tyrosine kinase in hamster cheek pouch microcirculation.
We studied the interactions between platelet-activating factor (PAF) and protein tyrosine kinase (PTK) in the modulation of microvascular responses in the hamster cheek pouch using intravital microscopy and computer-assisted image analysis. Changes in arteriolar diameter and in integrated optical intensity (IOI; an index of vascular permeability) were measured. Fluorescein isothiocyanate-labeled dextran 150 (FITC-Dx 150) served as a tracer for macromolecular transport. Genistein and tyrphostin 25, two PTK inhibitors, were applied topically in separate experiments. Pretreatment with 10(-4), 10(-6), and 10(-8) M genistein and with tyrphostin 25 at 10(-5) and 10(-7) M attenuated the maximal increment in mean IOI (+/- SE) induced by PAF at 10(-7) M (19.9 +/- 5.3, 21.5 +/- 4.5, 58.5 +/- 11.4, 28.7 +/- 7.6, and 35.0 +/- 10.9 vs. 70.7 +/- 8.9 units, respectively). Pretreatment with PTK inhibitors resulted in vasodilation but did not inhibit PAF-induced vasoconstriction. Our results suggest that PTK represents a biochemical pathway involved in the PAF modulation of microvascular permeability but not PAF modulation of arteriolar tone.
Kim
D
D
Department of Physiology, University of Medicine & Dentistry of New Jersey-New Jersey Medical School, Newark 07103.
Durán
W N
WN
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D002199:Capillary Permeability; D002396:Catechols / Q000494:pharmacology; D002610:Cheek; D006224:Cricetinae; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D009061:Mouth Mucosa / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D009570:Nitriles / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020032:Tyrphostins
D002396:Catechols; D007529:Isoflavones; D009570:Nitriles; D010972:Platelet Activating Factor; D020032:Tyrphostins; C060152:tyrphostin 47; D001120:Arginine; D019833:Genistein; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D011505:Protein-Tyrosine Kinases; D019331:NG-Nitroarginine Methyl Ester