Salutary effects of ATP-MgCl2 on altered hepatocyte signal transduction after hemorrhagic shock
Mahmoud, M.S.; Wang, P.; Chaudry, I.H.
American Journal of Physiology 272(6 Pt 1): G1347-G1354
1997
ISSN/ISBN: 0002-9513 PMID: 9227469 Document Number: 483695
Although previous studies indicate that hepatocyte P-2 purinoceptors, macrophage adenosine 3',5'-cyclic monophosphate (cAMP), and beta-adrenergic receptors decrease after hemorrhage and that administration of ATP-MgCl-2 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-MgCl-2 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-MgCl-2 (50 mu-mol/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 (IP-3) were determined. The results indicate that basal levels of cAMP decreased whereas IP-3 increased after hemorrhage and resuscitation. Receptor-dependent stimuli (i.e., glucagon and vasopressin) failed to elicit cAMP or IP-3 accumulation after hemorrhage. In contrast, receptor-independent stimulation was not impaired. ATP-MgCl-2 treatment, however, prevented the decreased basal levels of cAMP and IP-3 and the ability of hepatocytes to respond to receptor-dependent stimulation. Thus ATP-MgCl-2 treatment of animals after trauma-hemorrhage and resuscitation attenuates the impaired second messengers cAMP and IP-3 and their membrane transduction processes.