Inhibition of purified bovine milk lipoprotein lipase by propranolol and other β-adrenergic blockers in vitro

Abstract

Numerous clinical studies have shown that propranolol administration causes hypertriglyceridemia and a decrease in high-density lipoprotein in man. Although these findings have been attributed to diminution of triacylglycerol-rich lipoprotein catabolism by lipoprotein lipase, biochemical studies of the effects of propranolol on lipoprotein lipase activity in vitro have not been previously reported. We purified lipoprotein lipase from raw bovine skimmed milk and examined the effect of propranolol using as substrate phospholipid-stabilized, triolein emulsions containing purified human apolipoprotein C-II. These studies demonstrate that propranolol inhibits lipoprotein lipase activity. The inhibition was found to be noncompetitive with a K i for propranolol of 0.55 mM. In addition, propranolol was shown to bind to phospholipid-stabilized triolein emulsions reaching local concentrations at the particle surface many times higher than its bulk concentration. Metoprolol, timolol and practolol, which are less hydrophobic than propranolol, were less inhibitory. Atenolol was the weakest inhibitor of purified bovine lipoprotein lipase in vitro.