MORPHINE AND BILIARY TRACT FUNCTION
Abstract
The overall objective of this study was to determine whether chronic morphine exposure would alter the normal function of the biliary tract and/or alter bile composition. Adult guinea pigs were implanted with 4-5 morphine pellets (100 mg morphine) subcutaneously. Morphine (100-400 ug/kg, i.v.) induced longer sphincter of Oddi (SO) spasm in male morphine-treated guinea pigs (MTGP), as monitored by cessation of biliary tract perfusate. Morphine did not induce spasm when added to sphincter of Oddi (SO) isolated from MTGP. Responses of cholecystokinin (CCK) on bile flow were depressed in both female and male MTGP. Gall-bladder isolated from MTGP exhibited decreased CCK and acetylcholine responses. The observed increased SO spasms and depression of CCK responses should lead to stasis of bile flow. In bile stored in gall-bladders of male MTGP, the concentrations of bile acids and cholesterol but not phospholipids were lowered. In newly secreted bile, only phospholipid concentrations were altered (elevated). In bile stored in gallbladders from female MTGP, cholesterol levels were unchanged. However, the concentrations of bile acids and phospholipids were lowered by 70% resulting in a highly lithogenic bile. Cholesterol concentrations were elevated in bile secreted spontaneously after decholin. The other two bile constituents did not change. The concentration ratios between bile components in gallbladder bile and those in bile spontaneously secreted from the liver were significantly reduced in the MTGP vs. control. This observation implied that MTGP had a lesser capacity to concentrate bile than non-MTGP. These results indicate that chronic morphine exposure produced significant changes which result in the formation of a more lithogenic bile and stasis of bile, actions that favor gallstone formation. These results also indicate that further studies on the role of endogenous opiates on gallstone pathophysiology are warranted.
Degree
Ph.D.
Subject Area
Pharmacology
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