DOWN-REGULATION OF HEPATOCYTE P-2-PURINOCEPTOR BINDING-CAPACITY AFTERTRAUMA-HEMORRHAGE RESUSCITATION

Although P-2-purinoceptors play an Important role in the regulation of liver metabolism under normal conditions, it is not known if trauma-h emorrhage and resuscitation have any effects on such receptors. To stu dy this, we performed a 5-cm midline laparotomy (i.e., trauma induced) on rats and then bled them to and maintained them at a mean arterial pressure of 40 mmHg until 40% of maximum bleedout volume was returned in the form of Ringer lactate (RL). The animals were then resuscitated with 3x the volume of shed blood with RL over 45 min followed by 2x R L over 95 min. Hepatocytes were isolated at the time of maximum bleedo ut or at 0, 4, 17, and 27 h after the completion of crystalloid resusc itation. P-2-purinoceptor binding characteristics were determined in t he isolated hepatocytes by using [alpha-S-35]ATP. Scatchard analysis r evealed high- and low-affinity components of P-2-purinoceptors in hepa tocytes from sham-operated as well as hemorrhaged and resuscitated ani mals. The maximum binding capacity (B-max) of the high-affinity recept or component decreased at the time of maximum bleedout and at 4, 17, a nd 27 h after resuscitation. In addition to this, the B-max of low-aff inity receptor components also decreased at 4-27 h after resuscitation . In contrast, the dissociation constants of both receptor components were not altered. Because hemorrhagic shock produces abnormalities in glucose metabolism, the downregulation of hepatocyte P-2-purinoceptor B-max may be responsible for the altered glucose homeostasis under suc h conditions.