AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 4 770-G778, Copyright © 1997 by American Physiological Society
Nitric oxide and gallbladder motility in prairie dogs
H. Salomons, A. P. Keaveny, R. Henihan, G. Offner, A. Sengupta, W. W. Lamorte and N. H. Afdhal
Evans Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA.
In this study we evaluated the role of nitric oxide (NO) on gallbladder
motility in the normal prairie dog by 1) immunohistochemistry, 2) an
enzymatic assay for NO 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 x mg protein(-1) x 30
min(-1). Blockade of NOS activity in vivo using N(omega)-nitro-L-arginine
methyl ester resulted in an 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 Ca2+ channels. An exogenous nitrosothiol,
S-nitroso-N-acetyl-cysteine, abolished cholecystokinin (CCK) octapeptide
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 CCK and bethanechol.
