PLATELET-ACTIVATING-FACTOR STIMULATES PROTEIN-TYROSINE KINASE IN HAMSTER-CHEEK POUCH MICROCIRCULATION

We studied the interactions between platelet-activating factor (PAF) a nd protein tyrosine kinase (PTK) in the modulation of microvascular re sponses in the hamster cheek pouch using intravital microscopy and com puter-assisted image analysis. Changes in arteriolar diameter and in i ntegrated optical intensity (IOI; an index of vascular permeability) w ere measured. Fluorescein isothiocyanate-labeled dextran 150 (FITC-Dx 150) served as a tracer for macromolecular transport. Genistein and ty rphostin 25, two PTK inhibitors, were applied topically in separate ex periments. Pretreatment with 10(-4), 10(-6), and 10(-8) M genistein an d with tyrphostin 25 at 10(-5) and 10(-7) M attenuated the maximal inc rement in mean IOI (+/-SE) induced by PAF at 10(-7) M (19.9 +/- 5.3, 2 1.5 +/- 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 modulati on of arteriolar tone.