EFFECT OF SOME SULFONATE ANALOGS OF URSODEOXYCHOLIC ACID ON BILIARY LIPID SECRETION IN THE RAT

The effect of the sulfonate analogues of ursodeoxycholic acid, namely sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate (no rUDC-SO3Na) and sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulf onate (UDC-SO3Na), on biliary lipid secretion was studied in bile fist ula rats. During intravenous infusion of the two sulfonate analogues, bile flow and biliary lipid secretion were stimulated in a dose-depend ent manner. This suggests that the analogues exert an effect on biliar y lipid secretion comparable to that of the naturally occurring bile a cid, ursodeoxycholyltaurine (UDC-tau). The effects of norUDC-SO3Na and UDC-SO3Na on bile flow were similar but slightly smaller than that of UDC-tau. The output of bile salts was similar with both sulfonates bu t greater than that with UDC-tau. The infusion of norUDC-SO3Na or UDC- SO3Na induced cholesterol secretion and phospholipid secretion more si gnificantly than UDC-tau infusion. The increase in phospholipid secret ion was particularly pronounced during high-dose administration of nor UDC-SO3Na. Although norUDC-SO3Na stimulated cholesterol secretion more intensely than the other two bile salts, it also facilitated phosphol ipid output, perhaps as a compensatory mechanism, and the biliary chol esterol/phospholipid ratio was decreased to a greater extent by the su lfonates than by UDC-tau. Consequently, the administration of norUDC-S O3Na or UDC-SO3Na produces a more ''stable'' bile than UDC-tau, sugges ting that these sulfonates possess potential cholelitholytic activity.