Selective modifications in the de novo biosynthesis of retinal phospholipids and glycerides by propranolol or phentolamine.

The effects of propranolol or phentolamine on the metabolism of phospholipids, diacylglycerol, and triacylglycerol were studied in the bovine retina in vitro. Lipid labeling was followed during short-term incubation of intact bovine retinas with [U-14C]glycerol and [1-14C]palmitic acid. Each of these precursors was recovered in the appropriate lipid moiety. Most of the [14C]glycerol appeared progressively in triacylglycerol (TG) through the sequence from phosphatidic acid (PA) to diacylglycerol (DG). Labeled palmitate appeared in much lower quantities than labeled glycerol in all glycerolipids except phosphatidylcholine (PC). Propranolol and phentolamine greatly enhanced the [14C]glycerol specific activities of PA, phosphatidylinositol (PI), and phosphatidylserine (PS), whereas labeling in other glycerolipids was much lower than in controls. The labeling in TG with both precursors was found to be less than 50% of the control values; however, a late increase in DG labeling was observed. The effects of these drugs on broken cell preparations were also described, although lipid synthesis from labeled glycerol in these preparations was only 9% that of intact retinas. It appeared that an amphiphilic cationic structure was necessary to produce these drug effects; propranolol glycol, the hydrophobic moiety of propranolol, did not elicit the same effects. It is suggested that, among other changes, the drugs inhibited phosphatidate phosphohydrolase and redirected the flux predominantly toward PI. Support for the proposed multiple lipid effects elicited by these drugs was provided by the dual changes found in the labeling of DG.