CHANGES OF ALPHA(1)-ADRENERGIC RECEPTORS IN HUMAN LIVER DURING INTRAABDOMINAL SEPSIS

We studied changes in alpha(1)-adrenergic receptors in human liver pla sma membranes during intraabdominal sepsis using [H-3]prazosin as a ra dioligand. Human liver tissues were obtained from nonseptic patients u ndergoing elective abdominal surgery (control group) and from patients with sepsis requiring laparotomy as a therapeutic measure (septic gro up). Septic patients were further divided into three subgroups on the basis of septic severity scores: mild sepsis (<21), moderate sepsis (2 2 to 32) and severe sepsis (>33). Plasma membranes were prepared by me ans of sucrose gradient centrifugation and were purified fivefold on t he basis of the enrichment of the activity of the marker enzyme, 5'-nu cleotidase. [SH]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 sev ere 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 moder ate sepsis (n = 4), 129.1 +/- 18.3 for severe sepsis [n = 5]). We foun d a significant inverse correlation (r = 0.85, p < 0.01) between chang es in the densities of alpha(1)-adrenergic receptors and septic severi ty scores. These data indicate that alpha(1)-adrenergic receptors in h uman liver plasma membranes undergo dynamic changes during the develop ment 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 alpha(1)-adrenergic receptor densities in huma n liver plasma membranes can be increased or decreased during the prog ression of septic shock, successful therapeutic interventions that aim to ameliorate glucose dyshomeostasis by way of alpha(1)-adrenergic re ceptor mediation may depend on appropriate timing of when intervention s are given. These findings thus may contribute to a better remedy for hepatic glucose dyshomeostasis during sepsis.