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Mitogen‐Activated Protein Kinases Regulate Platelet‐Activating Factor‐Induced Hyperpermeability
Author(s) -
YU PENG,
HATAKEYAMA TAKUYA,
ARAMOTO HARUO,
MIYATA TETSURO,
SHIGEMATSU HIROSHI,
NAGAWA HIROKAZU,
HOBSON ROBERT W.,
DURÁN WALTER N.
Publication year - 2005
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680500301706
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , in vivo , kinase , microbiology and biotechnology , chemistry , platelet activating factor , protein kinase a , mapk cascade , biology , endocrinology
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 μM and 30 μM 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.