Changes in alpha-adrenergic receptors in dog livers during endotoxic shock.
The effects of endotoxin administration on alpha-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 Kd (dissociation constant) of the high-affinity component was increased by 32.5% (0.4 +/- 0.04 nM for control vs 0.53 +/- 0.06 nM for endotoxic; P less than 0.05) with no significant change in the Kd for the low-affinity component (3.0 +/- 0.44 nM for control vs 3.4 +/- 0.44 nM 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 less than 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 less than 0.05) 2 hr after endotoxin injection. The competitive inhibition studies show that the apparent Kd values for (-)-epinephrine, (-)-norepinephrine, and prazosin were increased 15, 13, and 25 times, respectively, with no significant change in the apparent Kd values for yohimbine or phentolamine 2 hr postendotoxin. These data demonstrate that the binding affinity of the high-affinity component and the number of alpha-adrenergic receptor binding sites were decreased in endotoxic shock. A modification of the alpha-adrenergic receptors in dog livers induced by endotoxin administration may play an important role in the development of hepatic glucose dyshomeostasis during shock.
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D004088:Dihydroergotoxine / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism*
D004731:Endotoxins; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D004088:Dihydroergotoxine