Mechanism of endotoxin-induced reduction in the number of beta-adrenergic receptors in dog livers: role of phospholipase A.
The role of phospholipase A on the endotoxin-induced reduction in the number of beta-adrenergic receptors in dog liver plasma membranes was investigated. The results show that digestion of control liver plasma membranes with exogenous phospholipase A2 (0.2 unit/200 micrograms protein) decreased the specific binding of (-)-[3H]dihydroalprenolol by 37.3% (P less than 0.01) and reduced the number of receptor sites by 31.7% (P less than 0.05). These decreases in the specific binding and the number of beta-adrenergic receptors were completely reversible by the addition of phosphatidylcholine (0.2 mM). Endotoxin administration (2 hr postendotoxin) decreased the specific binding by 36% (P less than 0.05) and reduced the number of beta-adrenergic receptors by 33% (P less than 0.05), and these decreases were completely reversible by the addition of 0.2 mM phosphatidylcholine. Digestion of control liver membranes with exogenous phospholipase A2 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 beta-adrenergic receptors in dog livers during endotoxic shock are a result of phospholipase A activation.
D000818:Animals; D004285:Dogs; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D010740:Phospholipases / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012772:Shock, Septic / Q000378:metabolism
D004731:Endotoxins; D008563:Membrane Lipids; D010743:Phospholipids; D011943:Receptors, Adrenergic, beta; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2