Mechanism of endotoxin-induced reduction in the number of β-adrenergic receptors in dog livers: Role of phospholipase A

Abstract

The role of phospholipase A on the endotoxin-induced reduction in the number of β-adrenergic receptors in dog liver plasma membranes was investigated. The results show that digestion of control liver plasma membranes with exogenous phospholipase A 2 ( 0.2 unit 200 μ g protein) decreased the specific binding of (−)-[ 3H]dihydroalprenolol by 37.3% ( P < 0.01) and reduced the number of receptor sites by 31.7% ( P < 0.05). These decreases in the specific binding and the number of β-adrenergic receptors were completely reversible by the addition of phosphatidylcholine (0.2 m m). Endotoxin administration (2 hr postendotoxin) decreased the specific binding by 36% ( P < 0.05) and reduced the number of β-adrenergic receptors by 33% ( P < 0.05), and these decreases were completely reversible by the addition of 0.2 m m phosphatidylcholine. Digestion of control liver membranes with exogenous phospholipase A 2 decreased phosphatidylcholine and phosphatidylethanolamine levels by 50.6 and 51.2%, respectively, but increased lysophosphatidylcholine and lysophosphatidylethanolamine levels by 12- and 8.4-fold, respectively. Endotoxin administration decreased phosphatidylcholine and phosphatidylethanolamine contents by 21.4 and 23.8%, respectively, but increased lysophosphatidylcholine and lysophosphatidylethanolamine contents by 2.1- and 1.4-fold, respectively. In addition, endotoxin administration increased endogenous phospholipase A activity by 73.5%. Based on these results, it is suggested that the decreases in the specific binding and the number of β-adrenergic receptors in dog livers during endotoxic shock are a result of phospholipase A activation.