BILIARY LIPID OUTPUT BY ISOLATED-PERFUSED RAT LIVERS IN RESPONSE TO CHOLYL-LYSYLFLUORESCEIN

The biliary output of bile acids and lipids is tightly coupled. The ab ility of the natural bile acid glycocholate to trigger biliary lipid s ecretion was compared with that of the fluorescent bile acid analogue cholyl-lysylfluorescein (cholyl-lys-F). When administered as a 5 min p ulse of 2.5 mu mol/min to bile acid-depleted rat livers perfused under recycling conditions, glycocholate produced well-defined peaks of pho spholipid and cholesterol output, and of bile flow, which were coincid ent with the peak of bile acid output. Although cholyl-lys-F did trigg er biliary lipid secretion, its time course of appearance was delayed and well-defined peaks of output were not observed. However, the incre ased biliary output of phospholipid and cholesterol was coincident wit h that of bile acids and, as judged by phospholipid/bile acid and chol esterol/bile acid ratios, cholyl-lys-F was as effective as glycocholat e in triggering biliary lipid output. When administered to livers perf used under single pass conditions, perfusate to bile transfer of glyco cholate was >85% at infusion rates of up to 5 mu mol/min whereas trans fer of cholyl-lys-F showed saturation at infusion rates of >0.2 mu mol /min; the time course of biliary output of both bile acids was similar . Thus, under recycling conditions, cholyl-lys-F not taken up during f irst pass will be continually represented for transfer to bile, explai ning why bile acid and lipid output did not occur as well-defined peak s.