title: Studies with verapamil and nifedipine provide evidence for the presence in the liver cell plasma membrane of two types of Ca2+ inflow transporter which are dissimilar to potential-operated Ca2+ channels.
abstract: The addition of 500 microM verapamil or nifedipine to isolated hepatocytes incubated in the presence of 1.3 mM Ca2+ caused 20% inhibition of Ca2+ inflow as measured by the initial rate of 45Ca2+ exchange. No stimulation of 45Ca2+ exchange was observed in the presence of the Ca2+ agonist CGP 28392. An increase in the concentration of extracellular K+ from 6 to 60 mM (to depolarize the plasma membrane) increased the initial rate of 45Ca2+ exchange by 30%. In the presence of 60 mM K+, 400 microM verapamil inhibited the initiate rate of 45Ca2+ exchange by 50%. Verapamil and nifedipine completely inhibited vasopressin-induced Ca2+ inflow as determined by measurement of the initial rate of 45Ca2+ exchange and of glycogen phosphorylase a activity. This effect of verapamil was completely reversed by increasing the extracellular concentration of Ca2+. The concentrations of Ca2+ antagonist which gave 50% inhibition of vasopressin- or K+-stimulated Ca2+ inflow were in the range 50-100 microM, about 50-fold greater than the concentration which gave 50% inhibition of the beating of electrically-stimulated myocardial muscle cells. In the absence of vasopressin, verapamil caused a transient increase in glycogen phosphorylase a activity by a process which is largely independent of Ca2+. It is concluded that verapamil and nifedipine inhibit the transport of Ca2+ across the hepatocyte plasma membrane through a putative Ca2+ transporter which is activated by vasopressin and which differs in nature from potential-operated Ca2+ channels in excitable cells and from the Ca2+ transporter present in hepatocytes in the absence of hormone.
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D010762:Phosphorylase a / Q000378:metabolism; D051381:Rats; D014667:Vasopressins / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D007473:Ion Channels; D014667:Vasopressins; D014700:Verapamil; D010762:Phosphorylase a; D009543:Nifedipine; D002118:Calcium