The role of extracellular Ca2+ in the response of the hepatocyte to Ca2+-dependent hormones

S. K. Joseph, K. E. Coll, A. P. Thomas

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The influence of extracellular Ca2+ on hormone-mediated increases of cytosolic free Ca2+ ([Ca2+](i)) and phosphorylase activity was studied in isolated hepatocytes. In the presence of 1.3 mM extracellular Ca2+, the stimulation of phosphorylase activity produced by vasopressin or phenylephrine was maintained for 20-30 min. In contrast, the change in [Ca2+](i) under these conditions was more transient and declined within 3-4 min to steady state values only 70 ± 8 nM above the resting [Ca2+](i). Removal of the hormone from its receptor with specific antagonists caused a decline in [Ca2+](i) back to the orginial resting values. Subsequent addition of a second hormone elicited a further Ca2+ transient. If the antagonist was omitted, the second hormone addition did not increase [Ca2+](i) indicating that the labile intracellular Ca2+ pool remains depleted during receptor occupation. When extracellular Ca2+ was omitted, both the changes of [Ca2+](i) and phosphorylase a caused by vasopressin were transient and returned exactly to resting values within 3-4 min. The subsequent readdition of Ca2+ to these cells produced a further increase of [Ca2+](i) and phosphorylase activity which was larger than the changes observed upon Ca2+ addition to untreated cells. This reactivation of phosphorylase showed saturation kinetics with respect to extracellular Ca2+, was maximally stimulated within 1 min of vasopressin addition and was inhibited by high concentration of diltiazem. We conclude that entry of extracellular Ca2+ into the cell is required in order to obtain a sustained hormonal stimulation of phosphorylase activity and is responsible for the maintenance of a small steady state elevation of [Ca2+](i).

Original languageEnglish (US)
Pages (from-to)12508-12515
Number of pages8
JournalJournal of Biological Chemistry
Issue number23
StatePublished - 1985
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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