N-(2-Benzoyloxyethyl) norfenfluramine (S-780) was administered to rats by stomach tube at a dose of 50 mg kg-1 of body weight. Livers of the rats which were given an acute dose of the drug synthesized more triacylglycerol, phosphatidylcholine and phosphatidylethanolamine from [1,3-3H]glycerol and [14C]palmitate than did those of control rats. The measurements were made by injecting a mixture of the radioactive precursors into the portal veins of anaesthetized rats and freeze clamping a portion of the liver 1 min later. Diffferent results were obtained after treating rats daily with S-780 for 5 days. Liver slices from these rats synthesized less triacylglycerol and relatively more phosphatidylinositol plus phosphatidylserine from [3H]glycerol than did those of control rats. S-780 treatment depressed the hepatic synthesis of phosphatidylcholine and phosphatidylethanolamine as measured in vivo after intrapotal injection of [14C]palmitate and [3H]glycerol. Chronic treatment with S-780 also depressed food intake and lowered liver weight and body weight of rats fed the 41B diet. The results are discussed in relation to the effects of S-780 on the synthesis of glycerolipids.
Bile previously labeled with tritiated oleic acid (the main radioactivity was on bile phospholipids) was mixed with pure isolated phospholipids previously labeled with 14C oleic acid; this mixture was perfused during 6 or 23 hr into the duodenum of test rats bearing a bile fistula. At the time of decapitation, in the small intestine a large hydrolysis of the 14 C phospholipids was found. In contrast no bile phospholipid hydrolysis was observed. In the collected bile samples of the test rats, no 14C could be detected (this means a very large decrease of the 14C fatty acids specific activities by the body fatty acids), and the tritiated fatty acids specific activities were only 2.5-12 times lower than in the perfused bile. These results can be explained, asshming that the bile phospholipids enter in an entero-hepatic circulation and are preserved from the dilution in a large pool of lipids.
Mixtures of fresh bile of the rat and of isolated hepatic phospholipids (one or the other of these components having been labeled with 3H oleic acid) were incubated either with heated rat pancreatic juice, at 37 C during periods of 1 and 3 hr, or with snake venom, at 25 C during periods of 17 and 36 hr, as sources of phospholipase A 2. After incubation, tritiated free oleic acid was measured since this acid was in the 2 position of both phospholipidic substrates. With heated pancreatic juice, no significant enzymatic hydrolysis of the bile phospholipids occured, but isolated hepatic phosphohpids were readily attacked. With snake venom, the whole isolated hepatic phospholipids were very strongly hydrolyzed while biliary phospholipids were hydrolyzed to a much lesser extent.
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