Changes in beta-adrenergic receptors in dog livers during endotoxic shock

Abstract

The effects of endotoxin [Escherichia coli] administration on .beta.-adrenergic receptors in dog liver plasma membranes were studied using [3H]dihydroalprenolol as a radioactive ligand. Scatchard analysis revealed a 1 component binding characteristic in control and endotoxin-injected dogs. Kd increased by 60% (4.2 .+-. 0.5 nM for control vs. 6.7 .+-. 0.5 nM for endotoxic; P < 0.01) and Bmax (maximum binding capacity) decreased by 38% (600 .+-. 60 and 370 .+-. 70 fmol/mg protein for control and endotoxic, respectively; P < 0.01) 2 h following endotoxin administration. Competitive inhibition studies showed that, at 2 h postendotoxin, apparent Kd values for (-)-isoproterenol, (-)-epinephrine, and (-)-norepinephrine were increased by 14, 51 and 5 times, respectively. Endotoxin in vitro had a dose-dependent inhibitory effect on the specific binding of [3H]dihydroalprenolol and it also reduced the number of .beta.-receptors. Thus, endotoxin, in vivo and in vitro, decreased the binding affinity and the number of .beta.-adrenergic receptors in dog liver plasma membranes. A modification of the .beta.-adrenergic receptors in dog livers induced by endotoxin administration may play an important role in the development of hepatic glucose dyshomeostasis during shock.