Inhibition of p42 and p44 map kinase does not alter smooth muscle
contraction in swine carotid artery.
Gorenne, Isabelle, Xiaoling Su, and Robert S. Moreland.
Department of Physiology, MCP/Hahnemann School of Medicine,
Allegheny University of the Health Sciences, Graduate Hospital
Research Building, 415 S. 19th Street, Philadelphia, PA 19146
APStracts 5:0133H, 1998.
Caldesmon inhibits myosin ATPase activity; phosphorylation of
caldesmon reverses the inhibition. The caldesmon kinase is believed
to be mitogen-activated protein (MAP) kinase. MAP kinases are
activated during vascular stimulation but a cause and effect
relationship between kinase activity and contraction has not been
established. We examined the role of MAP kinase in contraction using
PD098059, an inhibitor of MAP kinase kinase (MEK). MAP kinase
activity was assessed using an anti-active MAP kinase antibody and
direct measurement of MAP kinase catalyzed phosphorylation of MBP95
-98. MAP kinase phosphorylation, stimulated by histamine (50 M) or
PDBu (0.1 M), was inhibited by PD098059 (100 M). PD098059 did not
alter the sensitivity or the maximal level of force in smooth muscle
stimulated by histamine or PDBu, nor did PD098059 affect contraction
of b-escin permeabilized tissue. Our data suggest that p44 and p42
MAP kinases are not involved in regulation of vascular smooth muscle
contraction. These results do not however preclude a role for other
isoforms of the MAP kinase family.
Received 8 January 1998; accepted in final form 24 March 1998.
APS Manuscript Number H6-8.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 24 April 1998