Progressive internalization of beta-adrenoceptors in the rat liver during different phases of sepsis.

Changes in the distribution of beta-adrenoceptors (beta ARs) in the plasma membrane and the light vesicle fractions of rat liver during different phases of sepsis were studied using [3H]dihydroalprenolol binding and photoaffinity labeling with [125I]iodocyanopindolol diazirine. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats exhibit an initial hypermetabolic (hyperglycemic) phase (9 h after CLP; early sepsis) followed by a hypometabolic (hypoglycemic) phase (18 h after CLP; late sepsis). The radioligand studies show that in the plasma membranes, the density of beta ARs was decreased by 28-32% and 46-69% during the early and the late phases, respectively, of sepsis. In the light vesicles, the density of beta ARs was increased by 25-30% and 30-35% during the early and the late phases, respectively, of sepsis. The total number of the receptor binding sites (the sum of that in plasma membrane plus light vesicle) was decreased by 11-12% and 21-35% during the early and the late phases, respectively, of sepsis. These results indicate that beta ARs were progressively internalized from surface membranes to the intracellular sites and, furthermore, they were underexpressed in the rat liver during the progression of sepsis. Since hepatic glucose metabolism is known to be regulated by catecholamines, in part, through beta AR mediation, an internalization/underexpression of hepatic beta ARs may play a role in the altered glucose homeostasis during sepsis, particularly in the late hypometabolic phase of sepsis.