Myosin light chain phosphorylation: modulation of basal and
agonist-stimulated venular permeability.
Yuan, Yuan, Qiaobing Huang, and H. Mac Wu.
Departments of Surgery and Medical Physiology and Microcirculation
Research Institute, Texas A & M University Health Science Center,
1901 South First Street, Building 4, Temple, Texas 76504
APStracts 3:0524H, 1996.
We have previously demonstrated that agonists increase microvascular
permeability through a phospholipase C-nitric oxide synthase
-guanylate cyclase cascade. The aim of this study was to further
investigate the downstream of the signaling pathway with a focus on
myosin light chain (MLC) phosphorylation. The apparent permeability
coefficient to albumin was measured in isolated coronary venules.
Under control conditions, the nitric oxide donor sodium
nitroprusside, as well as the cyclic GMP-dependent protein kinase
(PKG) activator 8-bromo-cyclic GMP, increased venular permeability
two- to three-fold. Similarly, activation of protein kinase C (PKC)
with phorbol myristate acetate significantly elevated permeability.
Inhibition of MLC phosphorylation with ML-7 significantly attenuated
the hyperpermeability responses to the agonists. Furthermore, ML-7
dose-dependently reduced basal venular permeability. Consistently,
inhibition of dephosphorylation with the protein phosphatase
inhibitor calyculin dramatically increased basal permeability. These
results suggest that 1) PKG and PKC play an important signaling role
in regulation of endothelial barrier function, and 2) MLC
phosphorylation contributes to basal and agonist-stimulated
microvascular permeability.
Received 2 July 1996; accepted in final form 24 October 1996.
APS Manuscript Number H589-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996