The role of bile in the regulation of exocrine pancreatic secretion.

As early as 1926 Mellanby (1) was able to show that introduction of bile into the duodenum of anesthetized cats produces a copious flow of pancreatic juice. In conscious dogs, Ivy & Lueth (2) reported, bile is only a weak stimulant of pancreatic secretion. Diversion of bile from the duodenum, however, did not influence pancreatic volume secretion stimulated by a meal (3,4). Moreover, Thomas & Crider (5) observed that bile not only failed to stimulate the secretion of pancreatic juice but also abolished the pancreatic response to intraduodenally administered peptone or soap. In man, the first report of a stimulating action of bile on pancreatic secretion was that of a patient with complete neoplastic obstruction of the common bile duct, published in 1942 by Lagerlof (6). Intraduodenal application of cattle bile increased pancreatic volume and bicarbonate secretion, whereas enzyme secretion was not influenced. It was not until the sixties that Forell et al. (7,8) rediscovered bile and bile salts as stimulants of exocrine pancreatic secretion in humans. After these first systematic studies, several investigators confirmed the stimulatory effect of bile and bile salts on exocrine pancreatic secretion (for example, Refs. 9-11), whereas others found no effect or even an inhibitory action (for example, Refs. 12, 13). In this review we would like to put forward the hypothesis that these controversial results may be primarily due to different experimental conditions. Several studies have been used with regard to the effect of intraduodenal bile and bile salts on basal or on exogenously stimulated pancreatic secretion by secretin or by secretin and cholecystokinin (CCK). Others have been performed on the endogenously stimulated pancreas by means of intestinally applied nutrient compounds probably interfering with the action of bile and bile salts. Diversion of bile and oral or intraduodenal application of bile-salt-binding resins (such as cholestyramine) may also provide approaches to study the role of bile and bile salts in the regulation of exocrine pancreatic secretion.