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

The effects of endotoxin administration on beta-adrenergic receptors in dog liver plasma membranes were studied using [3H]dihydroalprenolol as a radioactive ligand. The Scatchard analysis revealed a one-component binding characteristic both in control and endotoxin-injected dogs. The Kd (dissociation constant) value was increased by 60% (4.2 +/- 0.5 nM for control vs. 6.7 +/- 0.5 nM for endotoxic; P less than 0.01) and the Bmax (maximum binding capacity) was decreased by 38% (600 +/- 60 and 370 +/- 70 fmol/mg protein for control and endotoxic, respectively; P less than 0.01) 2 h following endotoxin administration. The competitive inhibition studies show that the apparent Kd values for (-)-isoproterenol, (-)-epinephrine, and (-)-norepinephrine were increased by 14, 51, and 5 times, respectively, 2 h postendotoxin. In addition, 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. These data demonstrate that endotoxin, both 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.