title: Prostaglandins suppress VLDL secretion in primary rat hepatocyte cultures: relationships to hepatic calcium metabolism.
abstract: In primary cultures of rat hepatocytes, prostaglandin E2 and prostaglandin D2 (PGE2 and PGD2) inhibited the secretion of very low density lipoprotein (VLDL)-associated apoB, triacylglycerol, and cholesterol. These effects were concentration-dependent and remained apparent for at least 3 days of culture without an effect on the apoB/triacylglycerol ratio of the secreted VLDL. Prostaglandins had no effect on the overall synthesis of triacylglycerol but triacylglycerol accumulated within the cells, without intracellular accumulation of apoB. PGE2, when added to the medium together with glucagon, increased the inhibition of VLDL secretion, compared to that observed with glucagon alone. However, PGE2 did not increase the stimulatory effect of glucagon on ketogenesis. Unlike glucagon, the prostaglandins did not inhibit fatty acid synthesis nor did they stimulate ketogenesis or production of cAMP. Thus, of all the parameters of hepatic lipid metabolism studied, PGE2 and PGD2 selectively affected VLDL. Selective inhibition of VLDL secretion was also observed with the calcium antagonist verapamil. The divalent cation ionophore A23187 also inhibited VLDL release but, in contrast, also inhibited fatty acid and cholesterol synthesis. The results suggest that VLDL secretion is modulated at some optimal cell calcium concentration that may be mediated selectively by agents such as prostaglandins.
authors.affiliation: Metabolic Research Laboratory, Radcliffe Infirmary, Oxford, United Kingdom.
authors.forename: O G
authors.initials: OG
authors.lastname: Björnsson
authors.forename: J D
authors.initials: JD
authors.lastname: Sparks
authors.forename: C E
authors.initials: CE
authors.lastname: Sparks
authors.forename: G F
authors.initials: GF
authors.lastname: Gibbons
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000502:physiology; D005227:Fatty Acids / Q000096:biosynthesis; D005934:Glucagon / Q000502:physiology; D006706:Homeostasis; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D015230:Prostaglandin D2 / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000096:biosynthesis; D014700:Verapamil / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D009829:Oleic Acids; D011453:Prostaglandins; D014280:Triglycerides; D019301:Oleic Acid; D000001:Calcimycin; D005934:Glucagon; D002784:Cholesterol; D014700:Verapamil; D000242:Cyclic AMP; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2; D015230:Prostaglandin D2; D002118:Calcium