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.