Angiotensin ii activated lipid signal transduction pathways in
angiotensin ii type 1 receptor transfected fibroblasts.
Wen, Yeshao, Myles C. Cabot, Eric Clauser, Stuart L. Bursten, Jerry L.
Nadler.
City of Hope Medical Center, Department of Diabetes and
Endocrinology, 1500 East Duarte Road, Shapiro 106, Duarte, CA 91010,
John Wayne Cancer Institute, Saint Johns Hospital and Health Center,
Santa Monica, CA 90404, Institut National de la Sante et de la
Recherche Medicale Unite 36, College de France, 3, rue d'Ulm 75005,
Paris France, Cell Therapeutics, Inc., Division of Lipid
Biochemistry, Seattle, WA 98119
APStracts 2:0100C, 1995.
A stable Chinese hamster ovary fibroblast line expressing the rat
vascular type 1a angiotensin II (AII) receptor was used to study the
lipid derived signal transduction pathways elicited by type 1a AII
receptor activation. AII caused a biphasic and dose-dependent
increase in diacylglycerol (DAG) accumulation with an initial peak at
15 sec (181+/-11% of control, p<0.02) and a second sustained peak at 5
-10 minutes (214+/-10% of control, p<0.02). The late DAG peak was
derived from phosphatidylcholine (PC) and the formation was blocked
by EGTA. AII also increased phosphatidic acid (PA) production nearly
4-fold by 7.5 min. In the presence of ethanol AII markedly increased
phosphatidylethanol (PEt) formation indicating activation of
phospholipase D (PLD). AII was shown to increase the mass of three
separate PA species, one of which apparently originated from DAG
kinase action on PC-PLC-produced DAG, providing evidence for PC-PLC
activity. AII also formed a third PA species which originated neither
from PLD nor DAG kinase. These results demonstrate that multiple
lipid signals propagated via collateral stimulation of phospholipases
C and D are generated by specific activation of the vascular type 1a
AII receptor.
Received 1 August 1994; accepted in final form 1 February 1995.
APS Manuscript Number C446-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 February 1995.