NITRIC-OXIDE AND GALLBLADDER MOTILITY IN PRAIRIE DOGS

In this study we evaluated the role of nitric oxide (NO) on gallbladde r motility in the normal prairie dog by 1) immunohistochemistry, 2) an enzymatic assay for NO synthase (NOS), and 3) an in vivo model to mea sure whole gallbladder tone and contractility. NOS was localized to ga llbladder mucosal cells by NADPH-diaphorase and polyclonal antibodies to a constitutive brain NOS. Gallbladder mucosal homogenates demonstra ted total NOS activity in the range of 578 +/- 115 pmol.mg protein(-1) .30 min(-1). Blockade of NOS activity in vivo using N-omega-nitro-L-ar ginine methyl ester resulted in an up to 80% increase in gallbladder t one from basal. A 40% increase in tone was seen with methylene blue, s uggesting that tone was maintained by both NO activation of guanylate cyclase and possibly direct effects on Ca2+ channels. An exogenous nit rosothiol, S-nitroso-N-acetyl-cysteine, abolished cholecystokinin (CCK ) octapeptide and bethanechol-stimulated gallbladder contraction. We c onclude that the prairie dog gallbladder contains constitutive NOS and synthesizes NO, which is important for the maintenance of basal gallb ladder tone and is an inhibitor of the contractile response of the gal lbladder to agonists such as CCK and bethanechol.