Effects of quinacrine on vasopressin-induced changes in glycogen phosphorylase activity, Ca²⁺ transport and phosphoinositide metabolism in isolated hepatocytes

In isolated hepatocytes, quinacrine (150-250 μM) inhibited vasopressin-induced increases in glucose release, glycogen phosphorylase a activity and ⁴⁵Ca²⁺ efflux; and glucagon-induced increases in glucose release and cyclic AMP formation. These results indicate that a phospholipase A₂ 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, ⁴⁵Ca²⁺ 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 A₂ [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.