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Effects of sympathomimetics and sympatholitics were studied on the biliary system of guinea-pigs (in vitro) and rabbits (in vitro and in vivo). Contractions and relaxations produced by sympathomimetic amines are mediated by alpha-excitatory and beta-inhibitoray adrenoceptors in the biliary system (gallbladder, common bile duct and sphinctor of oddi) of guinea-pigs. Sympathomimetic amines caused relaxations in the sphincter of oddi in rabbits (in vitro and in vivo) and responses were antagonized by alpha- and beta-blockade or a combination of both. Sympathomimetic amines caused contraction and relaxation on the common bile duct of rabbits. Transmural stimulation to guinea-pig gallbladder and rabbit common bile duct is mediated by cholinergic and adrenergic nerves, alpha-inhibitory adrenoceptor would thus be involved in the postanglionic cholinergic nerve endings in the gallbladder of guinea-pig. No difference was observed in mechanical responses to transmural stimulation in either the isolated sphincter of oddi or the duodenum of rabbits. It is concluded that the guinea-pig biliary system is functionally independent of the gastro-intestinal system and that the rabbit sphincter of oddi is functionally similar to the duodenal wall.

Effects of cisapride on the motility of the digestive tract in vivo in dogs and the guinea-pig intestine in vitro were studied. Cisapride (0.05-2.0 mg/kg, i.v.) produced an increase in amplitude of spontaneous contractions and basal tone in the stomach, duodenum, jejunum and proximal and distal colon in dogs. In some animals, however, it induced an inhibition with decrease in amplitude and tone. It also induced an increase in amplitude of contractions in the gallbladder and the sphincter of Oddi in dogs. The tone of the gallbladder was elevated by the same dose of cisapride, but the tone of the sphincter of Oddi was decreased. The drug produced a reverse response in some animals. These excitatory responses to cisapride were abolished by atropine (0.2 mg/kg, i.v.). Motility of the guinea-pig isolated ileum and colon was enhanced with an increase in their amplitude of contractions and basal tone at low concentrations of cisapride (10(-9)-10(-6)M) but it was inhibited at higher concentrations (10(-5)-10(-4)M). Atropine abolished the excitatory response of the ileum to cisapride in all cases. It abolished the excitation of the colon in some preparations but reduced only in some degree in the other. The inhibitory effect of cisapride on isolated preparations was unaffected by tetrodotoxin. From these results, it is concluded that cisapride enhances motility of the gastrointestinal tract and biliary tract by acting on myenteric cholinergic neurons and inhibits it by acting on the smooth muscle itself.

Alkaline and neutral elution techniques were applied to detect chemical carcinogens in biliary tract cancer using biliary tract epithelial cells in culture. Since biliary tract epithelial cells actively grow in culture, DNA breaks induced by carcinogens in the [14C] thymidine-prelabeled DNA could be detected as radioactivities in the eluted fractions. Our study demonstrated that aflatoxin B1, 20-methylcholanthrene and dimethylnitrosamine induced DNA single-strand breaks in the biliary tract epithelial cells by the use of this system. Cultured biliary tract epithelial cells/alkaline and neutral elution offers a sensitive and organ-specific model for the detection of chemical carcinogens to the biliary tract epithelium.