Inhibition of purified human postheparin lipoprotein lipase by beta-adrenergic blockers in vitro.
We examined the effects of five beta-adrenergic blockers on the hydrolysis of phosphatidylcholine-stabilized triolein particles by purified human postheparin lipoprotein lipase (PHLpL) in order to evaluate the possible role of direct inhibition as a mechanism of drug-induced hypertriglyceridemia. The relative inhibitory potencies were observed in the following order: propranolol much greater than pindolol greater than metoprolol greater than atenolol greater than nadolol. There was a positive correlation between the octanol/water partition coefficients of these agents and their inhibition of lipoprotein lipase, suggesting that hydrophobicity may be one of the major determinants for PHLpL inhibition. The amount of the beta-adrenergic blockers required to produce 50% inhibition of human PHLpL was much greater than that required to inhibit purified bovine lipoprotein lipase.
Kihara
S
S
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Kubo
M
M
Ikeda
N
N
Yokoyama
S
S
Matsuzawa
Y
Y
Tarui
S
S
Yamamoto
A
A
Hostetler
K Y
KY
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D014280:Triglycerides / Q000097:blood
D000319:Adrenergic beta-Antagonists; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D014280:Triglycerides; D006493:Heparin; D008071:Lipoprotein Lipase