Effects of quinacrine on vasopressin-induced changes in glycogen phosphorylase activity, Ca 2+ transport and phosphoinositide metabolism in isolated hepatocytes

Abstract

In isolated hepatocytes, quinacrine (150–250 μM) inhibited vasopressin-induced increases in glucose release, glycogen phosphorylase a activity and 45Ca 2+ efflux; and glucagon-induced increases in glucose release and cyclic AMP formation. These results indicate that a phospholipase A 2 enzyme sensitive to quinacrine is unlikely to be involved in the process by which vasopressin stimulates glycogen phosphorylase activity in the liver cell. In cells labelled with [ 3H]inositol, much lower concentrations of quinacrine (20–50 μM) inhibited the stimulation by vasopressin of the accumulation of [ 3H]inositol. The drug had little effect on vasopressin-induced accumulation of [ 3H]inositol mono-, bis- and trisphosphates. In the absence of vasopressin, higher concentrations of quinacrine caused a small stimulation of glycogen phosphorylase activity, 45Ca 2+ release and the formation of [ 3H]inositol polyphosphates. Quinacrine did not inhibit the degradation by liver homogenates of inositol 1-phosphate, inositol 4,5-bisphosphate or inositol 1,4,5-trisphosphate. It is concluded that concentrations of quinacrine comparable with those which inhibit phospholipase A 2 [G. J. Blackwell, W. G. Duncombe, R. J. Flower, M. F. Parsons and J. R. Vane, Br. J. Pharmac. 59, 353–366 (1977)] inhibit the stimulation by vasopressin of inositol utilization without significantly affecting coupling between hormone receptors and adenyl cyclase or phosphoinositide-specific phosphodiesterase, the action of the phosphodiesterase, and the degradation of inositol triphosphate.