Platelet-activating factor modulates microvascular transport by stimulation of protein kinase C.
To investigate the possible involvement of protein kinase C (PKC) in platelet-activating factor (PAF)-stimulated microvascular responses, PKC inhibitors, sphingosine (SPH), 1-(5-isoquino-linylsulfonyl)-3-methylpiperazine (iso H-7), and calphostin C, were applied topically to the hamster cheek pouch, and PAF-elicited changes in microvascular permselectivity and arteriolar constriction were evaluated. Pretreatment with 10(-6) M SPH, 10(-5) M SPH, or 10(-10) M iso H-7 significantly reduced 10(-7) M PAF-induced increase in fluorescein isothiocyanate-Dextran 150 clearance (2,677.3 +/- 397.3, 2,985.3 +/- 350.7, and 2,689.3 +/- 256.0 vs. 4,784.0 +/- 474.7 nl.60 min-1.g-1, respectively). Calphostin C at 10(-7) M attenuated 10(-8) M PAF-induced increase in clearance (2,156.9 +/- 353.3 vs. 3,841.6 +/- 260.9 nl.60 min-1.g-1). Permeability changes were also measured by integrated optical intensity (IOI). Pretreatment with 10(-6) M SPH, 10(-5) M SPH, or 10(-10) M iso H-7 attenuated the maximal increment in IOI induced by 10(-7) M PAF (2,024.0 +/- 364.4, 1,690.0 +/- 525.2, and 2,432.8 +/- 655.3 vs. 4,255.9 +/- 695.6 U, respectively). Direct stimulation of PKC by phorbol dibutyrate increased clearance in dose-dependent fashion. Similarly, activation of PKC with phorbol myristate acetate increased IOI values. The PAF-induced arteriolar constriction was not blocked by the PKC inhibitors. Our results suggest that PKC represents a biochemical pathway involved in the PAF modulation of microvascular permeability but not of arteriolar constriction.
Kobayashi
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Department of Physiology, UMDNJ New Jersey Medical School, Newark 07103-2714.
Kim
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Hobson
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Durán
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D000818:Animals; D001160:Arterioles / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D001775:Blood Circulation / Q000187:drug effects*; D006224:Cricetinae; D046911:Macromolecular Substances; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction
D046911:Macromolecular Substances; D010972:Platelet Activating Factor; D011493:Protein Kinase C