ATP-MGCL2 ADMINISTRATION NORMALIZES MACROPHAGE CAMP AND BETA-ADRENERGIC RECEPTORS AFTER HEMORRHAGE AND RESUSCITATION

Although ATP-MgCl2 attenuates the release of inflammatory cytokines an d restores the defective macrophage (M phi) antigen presentation funct ion after hemorrhage and resuscitation, it is not known whether admini stration of this agent after hemorrhage affects M phi adenosine 3',5'- cyclic monophosphate (cAMP) levels and beta-adrenergic receptors. To d etermine this, rats underwent a midline laparotomy (i.e., induction of trauma) and were then bled to and maintained at a mean arterial press ure of 40 mmHg until 40% of maximum bleedout volume was returned in th e form of Ringer lactate (RL). Animals were resuscitated with four tim es the volume of shed blood with RL, during and after which ATP-MgCl2 (50 mu mol/kg) or saline was administered over 95 min. At 1.5 h postre suscitation (i.e., 10 min after completion of ATP-MgCl2 infusion), per itoneal M phi and Kupffer cells were isolated, and cAMP levels were me asured by radioimmunoassay. beta-Receptor binding characteristics were also determined in isolated Kupffer cells. The results indicate that cAMP levels increased significantly in both peritoneal M phi and Kupff er cells after hemorrhage and resuscitation. Maximum binding capacity (B-max) of beta-receptors increased in Kupffer cells, suggesting that the elevated cAMP may be due to the increased beta-receptor B-max unde r such conditions. ATP-MgCl2 treatment, however, markedly decreased be ta-receptor B-max in Kupffer cells and cAMP in both peritoneal M phi a nd Kupffer cells, and the values were similar to shams. Thus normaliza tion of M phi cAMP levels and beta-receptor binding capacity by ATP-Mg Cl2 may contribute to the immunoenhancing effects of this agent observ ed after trauma-hemorrhage and fluid resuscitation.