AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 6 1347-G1354, Copyright © 1997 by American Physiological Society
Salutary effects of ATP-MgCl2 on altered hepatocyte signal transduction after hemorrhagic shock
M. S. Mahmoud, P. Wang and I. H. Chaudry
Center for Surgical Research, Brown University School of Medicine, Providence, Rhode Island, USA.
Although previous studies indicate that hepatocyte P2 purinoceptors,
macrophage adenosine 3',5'-cyclic monophosphate (cAMP), and beta-adrenergic
receptors decrease after hemorrhage and that administration of ATP-MgCl2
after hemorrhage normalizes these parameters, it is not known whether other
aspects of hepatocyte signal transduction processes, such as transmembrane
coupling, are also affected by hemorrhage and, if so, whether ATP-MgCl2 has
any beneficial effects on signal transduction. To study this, rats
underwent a 5-cm midline laparotomy (i.e., trauma induced) and were bled to
and maintained at a mean arterial pressure of 40 mmHg until 40% of a
maximum bleed-out volume was returned in the form of Ringer lactate (RL).
They were then resuscitated with three times the volume of shed blood with
RL over 45 min followed by two times the volume with RL+ATP-MgCl2 (50
mumol/kg body wt) or an equivalent volume of saline over 95 min.
Hepatocytes were isolated at 4 and 27 h after resuscitation, and basal as
well as stimulated levels of cAMP and inositol 1,4,5-trisphosphate (IP3)
were determined. The results indicate that basal levels of cAMP decreased
whereas IP3 increased after hemorrhage and resuscitation.
Receptor-dependent stimuli (i.e., glucagon and vasopressin) failed to
elicit cAMP or IP3 accumulation after hemorrhage. In contrast,
receptor-independent stimulation was not impaired. ATP-MgCl2 treatment,
however, prevented the decreased basal levels of cAMP and IP3 and the
ability of hepatocytes to respond to receptor-dependent stimulation. Thus
ATP-MgCl2 treatment of animals after trauma-hemorrhage and resuscitation
attenuates the impaired second messengers cAMP and IP3 and their membrane
transduction processes.
