Suppression of VLDL associated triacylglycerol secretion by both alpha- and beta-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 alpha- and beta-adrenoceptor agonists and antagonists on triacylglycerol secretion in freshly isolated rat hepatocytes. The inhibitory effect of epinephrine appeared at concentrations of more than 1 microM and reached a plateau at 100 microM. Epinephrine concentration for the half of the maximal bio-effect (EC(50)) was about 10 microM. Epinephrine at a concentration of 10 microM suppressed the secretion of triacylglycerol by 33% (P<or=0.01) and increased cellular content of triacylglycerol (18%, P<or=0.05) and total phospholipids (20%, P<or=0.05). Time course experiments for triacylglycerol secretion exhibited a linear relationship with a slope of 8.2+/-0.6 mug 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 microM) was abolished by the inclusion of the general alpha-adrenoceptor antagonist phentolamine (10 microM) and the specific alpha(1)-antagonist prazosin (1 microM) but not with the nonselective beta-antagonist propranolol (10 microM). Trifluoperazine an alpha-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 alpha-adrenoceptor agonist phenylephrine (10 microM) but also by the beta-agonist isoproterenol (10 microM). Dibutyryl-cAMP (0.1 mM) also inhibited the secretion of triacylglycerol by 30% (P<or=0.01). The results suggest that epinephrine inhibits the secretion of triacylglycerol from rat hepatocytes via the alpha(1)-adrenoceptor while stimulation of beta- as well as alpha-adrenoceptors can also exert a similar effect.
Rasouli
Mehdi
M
Department of Clinical Biochemistry, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran. mehdi.rasouli@yahoo.com
Zahraie
Mahin
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D011433:Propranolol; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine