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Ca2(+)-mobilizing hormones stimulate Ca2+ efflux from hepatocytes
S K Duddy1, G E Kass, S Orrenius
1Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
The Journal of Biological Chemistry
|December 15, 1989
Summary
Hormones rapidly lower elevated intracellular calcium (Ca2+) in hepatocytes by stimulating a Ca2+ efflux pathway. This mechanism terminates calcium transients, distinct from initial calcium release or influx.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Hepatocytes utilize intracellular calcium (Ca2+) signaling for various functions.
- The inositol 1,4,5-trisphosphate-sensitive Ca2+ pool plays a critical role in regulating cytosolic Ca2+ levels.
Purpose of the Study:
- To investigate the mechanism by which Ca2(+)-mobilizing hormones terminate elevated cytosolic Ca2+ in hepatocytes.
- To elucidate the role of Ca2+ efflux in regulating Ca2+ signaling dynamics.
Main Methods:
- Hepatocytes were treated with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) to mobilize the Ca2+ pool.
- Hepatocytes were subsequently exposed to Ca2(+)-mobilizing hormones (vasopressin, angiotensin II, ATP) or G-protein activators (NaF/AlCl3).
- Intracellular Ca2+ ([Ca2+]i) levels were monitored to assess the effects of treatments.
Main Results:
- tBuBHQ caused a sustained increase in [Ca2+]i.
- Ca2(+)-mobilizing hormones rapidly returned elevated [Ca2+]i to basal levels.
- Hormone-mediated Ca2+ removal was independent of cyclic nucleotides, protein kinase C, and arachidonic acid metabolites.
- The decrease in [Ca2+]i involved stimulation of a Ca2+ efflux pathway, not the Gi-protein.
Conclusions:
- Ca2(+)-mobilizing hormones actively regulate the termination of Ca2+ transients in hepatocytes.
- Hormones stimulate a Ca2+ efflux pathway to remove Ca2+ from the cytosol.
- This efflux pathway is crucial for terminating the Ca2+ signal initiated by Ca2+ release and influx.