Mitogen-activated protein kinases regulate platelet-activating factor-induced hyperpermeability.
OBJECTIVE
The authors tested the hypothesis that p42/44- (ERK-1/2) and/or p38-mitogen-activated protein kinases (MAPK) are in vivo regulatory elements in the platelet-activating factor (PAF) activated signaling cascade that stimulates microvascular hyperpermeability.


METHODS
FITC-dextran 70 was used as the macromolecular tracer for microvascular permeability in the mouse mesenteric fat tissue. Interstitial integrated optical intensity (IOI) was used as an index of permeability.


RESULTS
An application of 10(-7) M PAF increased IOI from 23.1 +/- 3.6 to 70.8 +/- 7.4 (mean +/- SEM). Inhibition of ERK-1/2 with 3 microM and 30 microM AG126 reduced IOI to 32.3 +/- 2.5. Similarly, inhibition of p38-MAPK with 6 nM, 60 nM and 600 nM SB203580 lowered IOI to 29.1 +/- 2.4.


CONCLUSIONS
The results demonstrate that ERK-1/2 and p38MAPK participate in the signaling cascade that regulates PAF-induced microvascular hyperpermeability in vivo.
Yu
Peng
P
Division of Vascular Surgery, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hatakeyama
Takuya
T
Aramoto
Haruo
H
Miyata
Tetsuro
T
Shigematsu
Hiroshi
H
Nagawa
Hirokazu
H
Hobson
Robert W
RW
Durán
Walter N
WN
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D050152:Intra-Abdominal Fat / Q000098:blood supply / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D010972:Platelet Activating Factor; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases