Synthesis of phosphatidylcholines in rat hepatocytes. Possible regulation by norepinephrine via an alpha-adrenergic mechanism.
The effect of norepinephrine on phosphatidylcholine and phosphatidylethanolamine formation was investigated in short-term incubations with freshly isolated rat hepatocytes. In the presence of dl-propranolol, norepinephrine decreases the incorporation of [methyl-14C]choline into phosphatidylcholines in a dose-dependent manner. At a concentration of 50 microM, norepinephrine (plus 20 microM propranolol) inhibits the incorporation of [methyl-14C]choline over a wide range of choline concentrations (59% inhibition at 5 microM choline; 34% inhibition at 1 mM choline). Norepinephrine also decreases the incorporation rates of [1-14C]palmitic acid and [1-14C]oleic acid into phosphatidylcholines. The effect of norepinephrine is mediated through an alpha-adrenergic receptor. Norepinephrine (plus propranolol) does not decrease the uptake or phosphorylation rate of [methyl-14C]choline. Pulse-label and pulse-chase studies indicate that the conversion rate of phosphocholine to CDP-choline, catalyzed by CTP:phosphocholine cytidylyltransferase, is diminished by norepinephrine. In contrast with the inhibitory effect of norepinephrine on phosphatidylcholine synthesis, this hormone stimulates the formation of phosphatidylethanolamines from [1,2-14C]ethanolamine. This increased incorporation rate is apparent at ethanolamine concentrations above 25 microM. A combination of norepinephrine and propranolol decreases, however, the synthesis of phosphatidylcholines from [1,2-14C]ethanolamine. The results indicate that alpha-adrenergic regulation dissociates the synthesis of phosphatidylcholines from that of phosphatidylethanolamines.
D000818:Animals; D002794:Choline / Q000378:metabolism; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D004983:Ethanolamines; D005227:Fatty Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011942:Receptors, Adrenergic, alpha; D014280:Triglycerides; D010643:Phenoxybenzamine; D019856:Ethanolamine; D011433:Propranolol; D002794:Choline; D009638:Norepinephrine