AJP - Regulatory, Integrative and Comparative Physiology, Vol 244, Issue 5 718-R723, Copyright © 1983 by American Physiological Society
Changes in beta-adrenergic receptors in dog livers during endotoxic shock
M. S. Liu and S. Ghosh
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.
