On the Mode of Action of Lipid-lowering Agents

Effects of an acetyl-coenzyme A carboxylase inhibitor and a sodium-sparing diuretic on aldosterone-stimulated sodium transport, lipid synthesis, and phospholipid fatty acid composition in the toad urinary bladder

“…did not alter the incorporation of labeled leucine or uridine into protein or RNA, respectively, in the presence or absence of aldosterone (Table II). It did, however, block the increase in both weight percentage of membrane phospholipid polyunsaturated fatty acids and [l4C]acetate incorporation into lipid usually seen after aldosterone action (Fig- others it is known that inhibits acetyl-CoA carboxylase in vitro by competitively binding to the isocitrate-activating site (Maragoudakis, 1970;Maragoudakis and Hankin, 1971). The drug, however, does not inhibit a number of glycolytic, citric acid cycle, and fatty acid synthesis enzymes (Maragoudakis, 1969).…”

“…It did, however, block the increase in both weight percentage of membrane phospholipid polyunsaturated fatty acids and [l4C]acetate incorporation into lipid usually seen after aldosterone action (Fig- others it is known that inhibits acetyl-CoA carboxylase in vitro by competitively binding to the isocitrate-activating site (Maragoudakis, 1970;Maragoudakis and Hankin, 1971). The drug, however, does not inhibit a number of glycolytic, citric acid cycle, and fatty acid synthesis enzymes (Maragoudakis, 1969). Results from rat mammary gland cell culture also indicate an effect of on acetyl-CoA carboxylase; although production of [14C]CC>2 and labeling of nonlipid material from [14C]acetate remains unchanged, lipogenesis is greatly reduced (Maragoudakis, 1971).…”

“…The drug, however, does not inhibit a number of glycolytic, citric acid cycle, and fatty acid synthesis enzymes (Maragoudakis, 1969). Results from rat mammary gland cell culture also indicate an effect of on acetyl-CoA carboxylase; although production of [14C]CC>2 and labeling of nonlipid material from [14C]acetate remains unchanged, lipogenesis is greatly reduced (Maragoudakis, 1971). Long-term feeding experiments in vivo, however, indicate that has other effects.…”

“…To gain further insight into the role of altered membrane lipid metabolism in aldosterone action and possibly help choose among these three alternatives, studies have been carried out with two inhibitors: 2-methyl-2-[/)-( 1,2,3,4-tetrahydro-1 -naphthyl)phenoxy]propionic acid ( ),1 an inhibitor of fatty acid biosynthesis (Maragoudakis, 1969), and amiloride, a specific inhibitor of mucosal Na+ entry in the intact bladder (Bentley, 1968).…”