Inositol 1,4,5-trisphosphate-, GTP-, arachidonic acid- and thapsigargin-mediated intracellular calcium movement in PANC-1 microsomes.
Inositol 1,4,5-trisphosphate (IP3)-, GTP-, arachidonic acid- and thapsigargin-mediated Ca2+ release from endoplasmic reticulum (ER)-enriched microsomes was studied in a PANC-1 cell line. IP3 maximally caused an approximately 20% release of actively accumulated Ca2+. This effect was completely blocked by heparin. In the presence of 3% polyethylene glycol (PEG), GTP maximally discharged about 60% of Ca2+ from the microsomes. This effect involved a GTP hydrolytic process, not the IP3-activated Ca2+ channel. Arachidonic acid maximally released approximately 80% of Ca2+ from PANC-1 microsomes. Metabolites of arachidonic acid did not appear to be involved in arachidonic acid-mediated Ca2+ release. However, other fatty acids also induced similar releasing effects suggesting that arachidonic acid-induced Ca2+ release appeared to be non-specific. Thapsigargin was shown to inhibit Ca2+ accumulation into and induce Ca2+ release from PANC-1 microsomes. The thapsigargin-releasable Ca2+ pool included the IP3- or arachidonic acid-sensitive pool. Studies on liposomes suggested that both arachidonic acid and thapsigargin did not exert either a Ca2+ ionophore-like or a membrane detergent-like effect. The present results have provided evidence for the existence of multiple non-mitochondrial Ca2+ pools in PANC-1 cells. These Ca2+ pools could be released by various Ca2+ mediators via different mechanisms.
Wu
L
L
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Katz
S
S
Brown
G R
GR
D016718:Arachidonic Acid / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008081:Liposomes / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014407:Tumor Cells, Cultured
D008081:Liposomes; D013729:Terpenes; D016718:Arachidonic Acid; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D002118:Calcium