Prostaglandins e2 and prostacyclin inhibit endothelin-1 secretion
from endothelial cells by stimulating the particulate form of
guanylate cyclase.
Razandi, Mahnaz, Ali Pedram, Tamar Rubin, and Ellis R Levin.
Departments of Medicine and Pharmacology, University of California,
Irvine, Irvine, California, 92717 and the Long Beach Veterans Affairs
Medical Center, Long Beach, California, 90822
APStracts 2:0401H, 1995.
Prostaglandins PGE2 and prostacyclin (PGI2) can cause vasodilation in
selective vascular beds and could act in part by inhibiting the
production of the vasoconstrictor, endothelin-1 (ET-1). We recently
reported that these prostanoids inhibit ET-1 production/secretion
from cultured endothelial cells via the generation of cGMP. It is
unclear whether this results from the stimulation of the particulate
(membrane) or soluble (cytosolic) form of guanylate cyclase (GC) and
if these effects are through an intermediate, such as nitric oxide.
PGE2 and PGI2 (PGs) each caused a 3- 4 fold increase in both membrane
and whole bovine aortic endothelial cell GC activity. The
stimulations were significantly reversed (80-90%) by the compound LY
83583, an antagonist to cGMP generation, but were unaffected by
methylene blue (MB), an inhibitor of nitric oxide-induced soluble GC.
In contrast, the PGs did not generate cGMP in cytosolic fractions.
The PGs inhibited ET-1 secretion from the intact cells, which was
significantly prevented by LY 83583, but not by MB. Neither PG
stimulated NO synthase activity, an indicator of NO generation. We
conclude that PGE2 and PGI2 are likely to inhibit ET-1 secretion
through the activation of the particulate guanylate cyclase,
identifying a novel mechanism by which the prostanoids signal in the
endothelial cell.
Received 14 March 1995; accepted in final form 30 August 1995.
APS Manuscript Number H243-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.