Exposure to depolarizing concentrations of K+ inhibits hormonally-induced calcium influx in rat liver.
The exposure of perfused rat livers to depolarizing concentrations of K+ (60 mM) by partial substitution of the NaCl in the medium with KCl induces glycogenolysis, respiratory changes and vasoconstriction. These responses were found to be inhibited 70-80% by 20 microM indomethacin and by 20 microM bromophenacyl bromide. This suggests that eicosanoids, namely prostaglandins, are involved in mediating these effects, and hence that the action of K+ involves primarily an effect on eicosanoid-producing cells (Kupffer and endothelial cells) within the liver. A 5 min pre-exposure of perfused livers to depolarizing concentrations of K+ (in the presence of indomethacin) was found to inhibit (by approx. 85%) the influx of Ca2+ induced by the co-administration of 10 nM glucagon and 10 nM vasopressin. A similar result was observed in isolated hepatocytes. The inhibition was probably not due to a decrease in the concentration of Na+ in the medium since the substitution of 80 mM NaCl with 80 mM choline chloride resulted in significantly less inhibition (30-40%). These results suggest that under these conditions the influx of Ca2+ in liver occurs through a pathway that is inhibited by high K+ concentration and/or a depolarization of the plasma membrane.
Altin
J G
JG
Department of Biochemistry, Faculty of Science, Australian National University, Canberra, A.C.T.
Biden
T J
TJ
Karjalainen
A
A
Bygrave
F L
FL
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*
D000098:Acetophenones; D008112:Liver Glycogen; D014667:Vasopressins; D005934:Glucagon; C006821:4-bromophenacyl bromide; D011188:Potassium; D002118:Calcium; D007213:Indomethacin