Inhibition of the liver cell receptor-activated Ca2+ inflow system by metal ion inhibitors of voltage-operated Ca2+ channels but not by other inhibitors of Ca2+ inflow.
The properties of the receptor-activated Ca2+ inflow system in the liver cell plasma membrane were compared with those of voltage-operated Ca2+ channels and receptor-operated Ca2+ channels present in other cell types by testing the susceptibility of the Ca2+ inflow system to inhibition by other metal ions and known inhibitors of Ca2+ movement across membranes. Co2+ inhibited Ca2+ inflow through the receptor-activated Ca2+ inflow system, as assessed by measurement of (a) the activation by extracellular Ca2+ (Cao2+) of glycogen phosphorylase in the presence of vasopressin and (b) 45Ca2+ exchange in the presence of the hormone. The concentration of Co2+ which gave half-maximal inhibition was 280 microM. The inhibition by Co2+ was reversed by high Cao2+. Co2+ did not inhibit basal Ca2+ inflow as measured by 45Ca2+ exchange in the absence of vasopressin. Zn2+, Cd2+, Ni2+ and Mn2+ each inhibited Ca2+ inflow through the receptor-activated Ca2+ inflow system. The concentrations of these ions which gave half-maximal inhibition were 10, 50, 220 and 400 microM, respectively. Little inhibition of receptor-activated Ca2+ inflow was observed in the presence of Sr2+ or Ba2+. However, substantial amounts of 90Sr2+ were taken up by hepatocytes. Rates of 90Sr2+ uptake increased from 0.5-8 nmol per min per mg wet wt. when the extracellular concentration of Sr2+ was varied from 0.25 to 2.5 mM. Sr2+ uptake was inhibited 50% by Cao2+ with half-maximal inhibition at 100 microM Cao2+, but was not inhibited by verapamil and was not stimulated by vasopressin. The movement of Ca2+ through the receptor-activated Ca2+ inflow system was not inhibited by high concentrations of each of a number of inhibitors of voltage-operated and receptor-operated Ca2+ channels and intracellular Ca2+ movement. It is concluded that while the susceptibility to inhibition by metal ions of the receptor-activated Ca2+ inflow system in the liver cell plasma membrane is similar to that of voltage-operated Ca2+ channels, there are significant differences between the liver cell receptor-activated Ca2+ inflow system and both voltage-operated Ca2+ channels and some other receptor-operated Ca2+ channels with respect to inhibition by organic compounds.
Hughes
B P
BP
Department of Medical Biochemistry, Flinders University School of Medicine, Bedford Park, Australia.
Barritt
G J
GJ
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002132:Calcium Radioisotopes; D002413:Cations, Divalent; D002462:Cell Membrane / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008670:Metals / Q000494:pharmacology*; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D013324:Strontium / Q000378:metabolism / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D002413:Cations, Divalent; D008670:Metals; D011956:Receptors, Cell Surface; D014667:Vasopressins; D001464:Barium; D003035:Cobalt; D006005:Phosphorylases; D002118:Calcium; D013324:Strontium