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

Abstract

The effects of endotoxin administration on α-adrenergic receptors in dog liver plasma membranes were studied using [ 3H]dihydroergocryptine as a radioactive ligand. The Scatchard analysis revealed a two-component binding characteristic both in control and endotoxin-injected dogs. The K d (dissociation constant) of the high-affinity component was increased by 32.5% (0.4 ± 0.04 n M for control vs 0.53 ± 0.06 n M for endotoxic; P < 0.05) with no significant change in the K d for the low-affinity component (3.0 ± 0.44 n M for control vs 3.4 ± 0.44 n M for endotoxic) 2 hr following endotoxin administration. The maximum binding capacity of the high-affinity component was decreased by 38.1% (460 ± 19.3 and 285 ± 14.8 fmole/mg protein for control and endotoxic, respectively; P < 0.01) and that of the low-affinity component was decreased by 34.2% (1050 ± 66.4 and 690 ± 44.6 fmole/mg protein for control and endotoxic, respectively; P < 0.05) 2 hr after endotoxin injection. The competitive inhibition studies show that the apparent K d values for (−)-epinephrine, (−)-norepinephrine, and prazosin were increased 15, 13, and 25 times, respectively, with no significant change in the apparent K d values for yohimbine or phentolamine 2 hr postendotoxin. These data demonstrate that the binding affinity of the high-affinity component and the number of α-adrenergic receptor binding sites were decreased in endotoxic shock. A modification of the α-adrenergic receptors in dog livers induced by endotoxin administration may play an important role in the development of hepatic glucose dyshomeostasis during shock.