Production and localization of cgmp and pge2 in sodium
nitroprusside-stimulated rat colonic ion transport.
Wilson, Keith T., Arie B. Vaandrager, Jan De Vente, Mark W. Musch,
Hugo R. De Jonge, and Eugene B. Chang.
Dept. of Medicine, University of Chicago, Chicago, IL, 60637, Dept.
of Biochemistry, Erasmus University, Rotterdam, Dept. of
Pharmacology, Free University, Amsterdam, The Netherlands
APStracts 2:0337C, 1995.
Nitrovasodilators (such as sodium nitroprusside (SNP)) release nitric
oxide (NO) and stimulate intestinal electrolyte transport (36).
However, the second messengers that are involved in this process are
unknown. NO stimulates soluble guanylate cyclase activity in other
tissues, but stimulation of this enzyme has not been previously
described in intestine. We report a 20 fold increase in cGMP
production by radioimmunoassay in colonic mucosal strips stimulated
with SNP. SNP also caused a significant increase in PGE2 release, but
did not stimulate release of the prostanoids thromboxane B2 or 6
-keto-PGF1[alpha]. Stimulation of isolated colonic crypts and the
remaining subepithelial mucosa demonstrated that the latter was the
major source of the increases in cGMP and PGE2. Immunostaining of
colonic mucosa revealed minimal basal cGMP immunoreactivity but large
increases in abundance, localizing to the subepithelium, after SNP
treatment. Under basal conditions, there was diffuse immunostaining
for constitutive NO synthase (cNOS) in both the epithelial and
subepithelial compartments, which was corroborated with NADPH
diaphorase staining. In conclusion, SNP as an NO-donor stimulates
production of cGMP and PGE2 from the subepithelium. NO may be an
important mediator of colonic secretion and other processes
predominantly via its direct effects on cells of the lamina propria.
Received 13 June 1995; accepted in final form 7 September 1995.
APS Manuscript Number C346-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.