Prostaglandins suppress VLDL secretion in primary rat hepatocyte cultures: relationships to hepatic calcium metabolism

In primary cultures of rat hepatocytes, prostaglandin E2 and prostaglandin D2 (PGE2 and PGDp) inhibited the secre- tion of very low density lipoprotein (VLDL)-associated apoB, tria- cylglycerol, 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, PGE, did not increase the stimulatory effect of glucagon on ketogenesis. Unlike glucagon, the prostaglandins did not inhibit fatty acid synthesis nor did they stimulate keto- genesis or production of CAMP. Thus, of all the parameters of hepatic lipid metabolism studied, PGEp and PGDp 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 synthe- sis. I The results suggest that VLDL secretion is modulated at some optimal cell calcium concentration that may be medi- aJed selectively by agents such as prostaglandins.-Bjornsson, 0. G., J. D. Sparks, C. E. Sparks, and G. E Gibbons. Prostaglandins suppress VLDL secretion in primary rat hepato- cyte cultures: relationships to hepatic calcium metabolism. J. Lipid Res. 1992. 33: 1017-1027.