Abstract
The effects of verapamil on basal and hormone-induced glycogenolysis, phosphorylase activation, 45Ca efflux and calcium content in isolated rat liver parenchymal cells were studied. The agent inhibited the stimulatory effects of epinephrine and phenylephrine on all these parameters, but did not modify the actions of vasopressin, glucagon, exogenously-added cAMP and low concentrations of the ionophore A23187. It inhibited calcium uptake due to high concentrations (>10-6 M) of A23187, but did not modify the activation of phosphorylase. Verapamil inhibited the binding of 4 x 10-8 M [3H]epinephrine to liver plasma membranes in the presence of the β-adrenergic blocker, propranolol. The concentration for half-maximal inhibition of binding (2 x 10-5 M) was very similar to that producing half-maximal inhibition of the effects of 4 x 10-8 M epinephrine on phosphorylase activation or calcium efflux in hepatocytes. Verapamil was without significant effect on the reaccumulation of calcium by cells previously depleted of calcium by treatment with EGTA. It is concluded that verapamil acts as an α-adrenergic antagonist in rat liver and has no detectable effects on transmembrane Ca2+ flux.
ACKNOWLEDGMENT We would like to thank Faith Brumley for her skilled and conscientious assistance.
- Copyright © 1979 by Academic Press, Inc.
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