Impairments in vasopressin-stimulated inositol lipid metabolism in hepatocytes of septic rats.
Vasopressin (VP)-stimulated 32P-inositol lipid metabolism was studied in hepatocytes obtained from rats rendered septic by cecal ligation and puncture. Basal 32P-phosphatidylinositol (PI) labeling, as well as its hormone-stimulated turnover, were greatly reduced in septic rats compared with sham-operated rats. The earliest VP-induced degradation of 32P-polyphosphoinositides (poly-PI) was greatly attenuated in septic rats. Moreover, while 32P-poly-PI labeling reached its lowest value by 60 sec of VP stimulation in cells from sham-operated rats, maximal changes in 32P-phosphatidylinositol 4,5-bisphosphate (32PIP2) occurred within 30 sec in septic rats. In contrast, the recovery of 32PIP2 labeling was more active in cells from septic rats, overcoming the impairment in its resynthesis triggered by surgical trauma in cells from sham-operated rats. The lower uptake of 32P into phosphatidic acid (PA) at the different time points analyzed was a sensitive indicator of the lower production of diacylglycerols from the VP-induced degradation of inositol phospholipids in septic rats. These observations support the idea that sepsis is associated with perturbations in the earliest events of the hepatocyte signal transmission pathway, namely, at the level of a receptor coupled to inositol lipid metabolism. Such perturbations are likely to be involved in the previously reported defective cell physiologic response to external hormone stimulation.
Rodriguez de Turco
E B
EB
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Spitzer
J A
JA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D007700:Kinetics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010712:Phosphatidic Acids / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018805:Sepsis / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology*
D001786:Blood Glucose; D007773:Lactates; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010743:Phospholipids; D014667:Vasopressins; D019344:Lactic Acid