Downregulation of hepatocyte P2-purinoceptor binding capacity after trauma-hemorrhage/resuscitation.
Although P2-purinoceptors play an important role in the regulation of liver metabolism under normal conditions, it is not known if trauma-hemorrhage and resuscitation have any effects on such receptors. To study 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 RL over 95 min. Hepatocytes were isolated at the time of maximum bleedout or at 0, 4, 17, and 27 h after the completion of crystalloid resuscitation. P2-purinoceptor binding characteristics were determined in the isolated hepatocytes by using [alpha-35S]ATP. Scatchard analysis revealed high- and low-affinity components of P2-purinoceptors in hepatocytes from sham-operated as well as hemorrhaged and resuscitated animals. The maximum binding capacity (Bmax) of the high-affinity receptor component decreased at the time of maximum bleedout and at 4, 17, and 27 h after resuscitation. In addition to this, the Bmax of low-affinity 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 P2-purinoceptor Bmax may be responsible for the altered glucose homeostasis under such conditions.
Department of Surgery, Michigan State University, East Lansing 48824.
M S
MS
Mahmoud
P
P
Wang
S R
SR
Hootman
S S
SS
Reich
I H
IH
Chaudry
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D015536:Down-Regulation; D006470:Hemorrhage / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D012151:Resuscitation; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate