LPS inhibits PI-phospholipase C but not PC-phospholipase D or phosphorylase activation by vasopressin and norepinephrine.
Rats were infused with endotoxin (50 micrograms/100 g body wt) for 3 h, and the parenchymal cells of the liver were maintained in primary culture for 1-3 h. The effects of vasopressin, norepinephrine, and glucagon on the activation of phosphatidylinositol (PI)-phospholipase C, phosphatidylcholine (PC)-phospholipase D, and glycogen phosphorylase a were investigated. Activation of PI-phospholipase C was markedly reduced, particularly with norepinephrine. This confirms that one of the early metabolic impairments seen in acute endotoxin treatment is inhibition of PI-phospholipase C activity. However, the ability of vasopressin, norepinephrine, and glucagon to stimulate glycogen phosphorylase a and PC-phospholipase D was not affected by this endotoxin treatment. We conclude that activation of phosphorylase a by vasopressin and norepinephrine is not entirely dependent on the activation of PI-phospholipase C and inositol trisphosphate formation.
Pittner
R A
RA
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1391.
Spitzer
J A
JA
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005934:Glucagon / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism / Q000502:physiology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010739:Phospholipase D / Q000378:metabolism / Q000502:physiology*; D010741:Phospholipases A / Q000378:metabolism / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology*
D004731:Endotoxins; D008070:Lipopolysaccharides; D010713:Phosphatidylcholines; D014667:Vasopressins; D005934:Glucagon; D010741:Phospholipases A; D010727:Phosphoric Diester Hydrolases; D010739:Phospholipase D; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D009638:Norepinephrine