EFFECTS OF URSODEOXYCHOLATE AND OTHER BILE-SALTS ON LEVELS OF RAT INTESTINAL ALKALINE SPHINGOMYELINASE - A POTENTIAL IMPLICATION IN TUMORIGENESIS

Previous studies showed that bile salts had a promoting effect on colo n cancer development and this effect was inhibited by ursodeoxycholate (UDC). We recently found that both human colorectal adenomas and carc inomas were associated with a specific decrease in alkaline sphingomye linase activity. In this work, we compared the effects of ursodeoxycho late and other bile salts on the levels of rat intestinal alkaline sph ingomyelinase both in the intestinal loops and after oral administrati on, Bile salts at different concentrations were injected into intestin al loops and the dissociation of alkaline sphingomyelinase from the mu cosa was assayed, We found that bile salts, including taurocholate, ta urodeoxycholate, glycocholate, glycochenodeoxycholate, and 3-(3-cholam idopropyl dimethylammonio)-1-propanesulonate (CHAPS), dose dependently dissociated alkaline sphingomyelinase from the intestinal mucosa, UDC alone did not dissociate the enzyme but significantly inhibited the d issociation caused by other bile salts and CHAPS, Feeding rats with 0. 3% (w/w) taurocholate for four days decreased peak activity of intesti nal alkaline sphingomyelinase by 39% and total activity in the intesti ne by 20% and increased the output of the enzyme in the feces, In cont rast, feeding 0.3% (w/w) UDC for four days increased the peak activity of alkaline sphingomyelinase in the small intestine by 87% and the ac tivity in the colon by 187%. The total activity of alkaline sphingomye linase was increased by 80% and the output of the enzyme in the feces was only slightly increased by UDC administration, The changes in alka line phosphatase after feeding taurocholate and UDC were much smaller. Our results indicate that UDC and other bile salts have different eff ects on the levels of alkaline sphingomyelinase? which may be implicat ed in their different influences on cancer development reported previo usly.