Perturbation of transmembrane signaling mechanisms in acute and chronic endotoxemia.
Our results reviewed here may be summarized as follows: 1. Continuous endotoxemia significantly interferes with Ca2+-dependent information flow in the liver. 2. The subcellular sites where these molecular lesions can be localized include: a.) the plasma membrane-there are effects at the level of alpha 1-adrenergic and vasopressin binding, and also in the coupling of receptor activation to inositol lipid metabolism in terms of PIP2 degradation and resynthesis b.) the endoplasmic reticulum in terms of Ca2+ release and PI synthesis. Another one of the sequelae of Ca2+-associated receptor activation, namely, cytosolic ionized Ca2+ concentration is also affected. 3. Finally, in addition to seeing the impact of acute or continuous endotoxemia at the level of receptor activation and signal generation, we can also document alterations in the expression of physiologic function subserved by these Ca2+- and inositol lipid-associated signaling processes--i.e. in glycogen phosphorylase activity-being consistent with the above described changes. In conclusion, we state that a causal link is shown between receptor binding, agonist-induced phosphoinositide hydrolysis, intracellular Ca2+ mobilization and activation of phosphorylase a in the liver, suggesting that these alterations may underlie some of the metabolic consequences of chronic sepsis.
D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002908:Chronic Disease; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D010762:Phosphorylase a / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D017483:Receptors, Vasopressin; D014667:Vasopressins / Q000494:pharmacology
D004731:Endotoxins; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D010762:Phosphorylase a; D002118:Calcium