BILIARY PHOSPHOLIPASES IN THE PRAIRIE DOG-MODEL FOR CHOLESTEROL CHOLELITHIASIS

Lysolecithin has been implicated as a contributing factor in the patho genesis of cholecystitis and cholesterol cholelithiasis. The phospholi pases are key enzymes in the generation of a number of metabolites inc luding lysolecithin, but conflicting reports exist concerning the pres ence of these enzymes in the biliary tract. In this study, measurement of phosphatidylcholine-specific phospholipase activity by means of th e hydrolysis of radiolabeled phosphatidylcholine (100 nmol) by 90 mu g of homogenate protein during a 60-min incubation demonstrated substan tial enzyme activities in gastric fundus and distal ileum (90% and 70% hydrolysis, respectively), whereas activity was virtually undetectabl e in gallbladder mucosa (0.7% hydrolysis). Additional studies were con ducted in prairie dogs fed diets high in cholesterol or with trace amo unts of cholesterol using homogenates of gallbladder mucosa, seromuscu laris and full-thickness tissue, as well as samples of hepatic and gal lbladder bile. The only hydrolytic activity in excess of blank values that was detected was a highly variable phospholipase A, activity in s everal gallbladder biles from animals given diets with both low levels and high levels of cholesterol, with the enzyme activities of the two dietary groups being similar. These results demonstrate that prairie dog gallbladder contains extremely low levels of phospholipase activit y, in marked contrast to other gastrointestinal tissues. However, ther e was evidence of a phospholipase A(2) activity in gallbladder bile. I n light of the low activity in gallbladder tissue, the source of this enzyme appears to be the liver and not the gallbladder. The fact that hydrolytic activity after cholesterol feeding was similar to that in c ontrol animals suggests that the increases in lysolecithin concentrati on in gallbladder bile that occur during early cholelithiasis may resu lt from stasis rather than from an increased hepatic secretion of phos pholipase.