Regulation of liver lipase. II. Involvement of the alpha 1-receptor

Abstract

The effects of different adrenergic agents on high density lipoprotein (HDL) cholesterol concentration and on the neutral NaCl-resistant triacylglycerol hydrolase (liver lipase) activity of the liver were studied in rats. Treatment of rats with the beta-blockers metoprolol, atenolol or propranolol led to a lowering of the HDL-cholesterol (esterified and non-esterified) content. The alpha 1-antagonist prazosin had no effect. Administration of norepinephrine for 10 days resulted in an increase of HDL non-esterified cholesterol. This effect of norepinephrine was largely abolished by prazosin, but not by propranolol. In normal rats the liver lipase activity was not influenced by alpha- or beta-blockade. Adrenergic stimulation, either short-term (by diethyl ether stress) or long-term (by norepinephrine treatment), led to a lowered liver lipase activity. The lipase activity was restored by prazosin but not by propranolol. The apparent involvement of the alpha 1-receptor in the regulation of liver lipase activity was further studied in vitro. Blockade of alpha- or beta-receptors with prazosin or propranolol did not affect the secretion of the liver lipase activity by isolated parenchymal liver cells. Stimulation of alpha- or beta-receptors by epinephrine led to a lower secreted lipase activity. Selective stimulation by isoprenaline had no effect. The effect of epinephrine could be abolished by prazosin but not by propranolol. Vasopressin and the calcium ionophore A23187 also lowered the secretion of liver lipase activity in vitro. Glucagon and/or the phosphodiesterase inhibitor Ro 20-1724 had no effect. These results indicate an involvement of the alpha 1-receptor in the regulation of liver lipase activity at the level of synthesis or secretion of the lipase. The effect of the alpha 1-receptor is presumably mediated through changes in the intracellular free calcium concentration. The effect of adrenergic modulation on HDL-cholesterol concentrations can partly be explained through modification of the liver lipase activity.