Suppression of VLDL associated triacylglycerol secretion by both α- and β-adrenoceptor agonists in isolated rat hepatocytes

The signal transduction pathways of intracellular calcium and adenosin 3′,5′-cyclic monophosphate (cAMP) participate in the regulation of intrahepatic metabolism of very low density lipoproteins (VLDL). The adrenoceptors are linked to calcium and cAMP signal transduction pathways so it is proposed that they may be involved in the regulation of VLDL secretion. The current study is designed to test the effects of α- and β-adrenoceptor agonists and antagonists on triacylglycerol secretion in freshly isolated rat hepatocytes.The inhibitory effect of epinephrine appeared at concentrations of more than 1 μM and reached a plateau at 100 μM. Epinephrine concentration for the half of the maximal bio-effect (EC50) was about 10 μM. Epinephrine at a concentration of 10 μM suppressed the secretion of triacylglycerol by 33% (P ≤ 0.01) and increased cellular content of triacylglycerol (18%, P ≤ 0.05) and total phospholipids (20%, P ≤ 0.05). Time course experiments for triacylglycerol secretion exhibited a linear relationship with a slope of 8.2 ± 0.6 μg triacylglycerol/3 h mg cell protein. In the presence of epinephrine, cellular triacylglycerol and total phospholipids were slightly but significantly higher than the respective control at all points of time examined.The inhibitory effect elicited by epinephrine (10 μM) was abolished by the inclusion of the general α-adrenoceptor antagonist phentolamine (10 μM) and the specific α1-antagonist prazosin (1 μM) but not with the nonselective β-antagonist propranolol (10 μM). Trifluoperazine an α-adrenoceptor antagonist and anticalmodulin agent, concealed the inhibitory effect of epinephrine in a concentration dependent manner, whereas theobromine a cAMP-phosphodiestrase inhibitor did not have any significant effect. The secretion of triacylglycerol was decreased not only by the α-adrenoceptor agonist phenylephrine (10 μM) but also by the β-agonist isoproterenol (10 μM). Dibutyryl-cAMP (0.1 mM) also inhibited the secretion of triacylglycerol by 30% (P ≤ 0.01). The results suggest that epinephrine inhibits the secretion of triacylglycerol from rat hepatocytes via the α1-adrenoceptor while stimulation of β- as well as α-adrenoceptors can also exert a similar effect.