Nitric oxide and gallbladder motility in prairie dogs.
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.
Salomons
H
H
Evans Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA.
Keaveny
A P
AP
Henihan
R
R
Offner
G
G
Sengupta
A
A
Lamorte
W W
WW
Afdhal
N H
NH
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D015153:Blotting, Western; D002766:Cholecystokinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012589:Sciuridae
D004791:Enzyme Inhibitors; D018723:Bethanechol; D009569:Nitric Oxide; D002766:Cholecystokinin; D019001:Nitric Oxide Synthase; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester