Action of phenobarbital and carbon tetrachloride on hepatic microsomal inosine diphosphatase in the rat.

Pretreatment of rats with phenobarbital decreased the in vitro activity of liver microsomal inosine diphosphatase, whereas CCl4 caused an opposite effect. These actions were essentially abolished when the activity of the enzyme was assayed in the presence of optimal concentrations of triton X-100. The detergent was shown to activate and solubilize the enzyme along with membrane protein and phospholipids. During solubilization there was a tendency towards a greater phosphatidylcholine and lower phosphatidylethanolamine content in triton-soluble membranes. Microsomes of phenobarbital-treated rats were more resistant to triton solubilization, whereas those from CCl4-treated rats were more susceptible than the controls. These results demonstrated a loose association between the enzyme and the endoplasmic reticulum and that phenobarbital or CCl4 altered the activity of IDP-ase probably by affecting the binding of the enzyme to the structure skeleton of the membrane. The role of phospholipid changes in the stability of microsomal membranes is discussed.