Nitric oxide and gallbladder motility in the prairie dog.
Salomons, Howard, Andrew P. Keaveny, Robert Henihan, Gwynneth Offner,
Ashok Sengupta, Wayne W. Lamorte, and Nezam H. Afdhal.
Section of Gastroenterology, Thorndike Memorial Laboratories and
Evans Dept. of Medicine, # Division of Pediatric Gastroenterology and
Nutrition and Department of Surgery, Boston University School of
Medicine, Boston, MA 02118
APStracts 3:0251G, 1996.
In this study, we evaluated the role of nitric oxide on gallbladder
motility in the normal prairie dog by 1) immunohistochemistry; 2) an
enzymatic assay for nitric oxide synthase ( NOS); and 3) an in-vivo
model to measure whole gallbladder tone and contractility. NOS was
localized to gallbladder mucosal cells by NADPH-diaphorase and
polyclonal antibodies to a constitutive brain NOS. Gallbladder
mucosal homogenates demonstrated total NOS activity in the range of
578 + 115 pmol/mg protein/ 30 min. Blockade of NOS activity in vivo
using N_-Nitro-L-Arginine Methyl Ester resulted in up to 80% increase
in gallbladder tone from basal. A 40% increase in tone was seen with
methylene blue suggesting that tone was maintained by both NO
activation of guanylate cyclase and possibly direct effects on
calcium channels. An exogenous nitrosothiol, s-nitroso-n-acetyl
cysteine abolished cholecystokinin octapepeptide and bethanechol
stimulated gallbladder contraction. We conclude that the prairie dog
gallbladder contains constitutive NOS and synthesizes NO which is
important for the maintenance of basal gallbladder tone and is an
inhibitor of the contractile response of the gallbladder to agonists
such as cholecystokinin and bethanechol.
Received 25 January 1996; accepted in final form 4 November 1996.
APS Manuscript Number G37-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996