Changes of α1-adrenergic receptors in human liver during intraabdominal sepsis



We studied changes in α1-adrenergic receptors in human liver plasma membranes during intraabdominal sepsis using [3H]prazosin as a radioligand. Human liver tissues were obtained from nonseptic patients undergoing elective abdominal surgery (control group) and from patients with sepsis requiring laparotomy as a therapeutic measure (septic group). Septic patients were further divided into three subgroups on the basis of septic severity scores: mild sepsis (<21), moderate sepsis (22 to 32) and severe sepsis (>33). Plasma membranes were prepared by means of sucrose gradient centrifugation and were purified fivefold on the basis of the enrichment of the activity of the marker enzyme, 5′-nucleotidase. [3H]prazosin-binding studies show that the maximal binding capacity was increased by 49.6% (p <0.01) in mild sepsis, relatively unchanged in moderate sepsis and decreased by 33.4% (p < 0.05) in severe sepsis (in femtomoles per milligram: 193.7 ± 5.7 for control [n = 6], 289.8 ± 23.4 for mild sepsis [n = 4], 192.3 ± 16.3 for moderate sepsis (n = 4), 129.1 ± 18.3 for severe sepsis [n = 5]). We found a significant inverse correlation (r = 0.85, p < 0.01) between changes in the densities of α1-adrenergic receptors and septic severity scores. These data indicate that α1-adrenergic receptors in human liver plasma membranes undergo dynamic changes during the development of sepsis — that is, the receptor number increased in mild sepsis, returned to a normal level in moderate sepsis and finally decreased in severe sepsis. Because α1-adrenergic receptor densities in human liver plasma membranes can be increased or decreased during the progression of septic shock, successful therapeutic interventions that aim to ameliorate glucose dyshomeostasis by way of α1-adrenergic receptor mediation may depend on appropriate timing of when interventions are given. These findings thus may contribute to a better remedy for hepatic glucose dyshomeostasis during sepsis. (HEPATOLOGY 1994;20:638-642).