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

Abstract

We studied changes in alpha 1-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 alpha 1-adrenergic receptors and septic severity scores. These data indicate that alpha 1-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.(ABSTRACT TRUNCATED AT 250 WORDS)