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Preparation of Pancreatic Acinar Cells for the Purpose of Calcium Imaging, Cell Injury Measurements, and Adenoviral Infection
10:39

Preparation of Pancreatic Acinar Cells for the Purpose of Calcium Imaging, Cell Injury Measurements, and Adenoviral Infection

Published on: July 5, 2013

FK506 induces biphasic Ca2+ release from microsomal vesicles of rat pancreatic acinar cells

Terutaka Ozawa1

  • 1Department of Physiology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. teozawa@mail.tains.tohoku.ac.jp

International Journal of Molecular Medicine
|June 21, 2006
PubMed

Insights

The immunosuppressant FK506 triggers a biphasic release of calcium from rat pancreatic cells, involving both ryanodine and IP3 receptors. This study reveals dual FK506-induced calcium release mechanisms in pancreatic endoplasmic reticulum.

Area of Science:

  • Cell Biology
  • Pharmacology
  • Biochemistry

Background:

  • Immunosuppressant FK506 affects cellular calcium signaling.
  • Microsomal calcium release is crucial in pancreatic acinar cell function.
  • Understanding drug-induced calcium dynamics is vital for therapeutic development.

Purpose of the Study:

  • To investigate the effect of FK506 on microsomal calcium (Ca2+) release in rat pancreatic acinar cells.
  • To elucidate the mechanisms underlying FK506-induced Ca2+ release.
  • To determine the involvement of specific calcium channels in this process.

Main Methods:

  • Utilized ATP-dependent 45Ca2+ uptake assays in isolated microsomal vesicles.
  • Administered varying concentrations of FK506 to assess dose-dependent effects.
  • Investigated the influence of cyclic ADP-ribose (cADPR) and heparin on FK506-induced Ca2+ release.
  • Examined the effect of inositol 1,4,5-trisphosphate (IP3) following FK506 treatment.

Main Results:

  • FK506 induced a dose-dependent and biphasic release of Ca2+ from microsomal vesicles.
  • Two affinity-dependent mechanisms were identified: high-affinity (Km=0.47 microM) and low-affinity (Km=55 microM).
  • cADPR enhanced FK506-induced release, while heparin inhibited it, suggesting ryanodine receptor involvement.
  • IP3 did not induce further Ca2+ release after FK506 treatment, indicating distinct pathways.

Conclusions:

  • FK506 activates two distinct Ca2+ release pathways in rat pancreatic endoplasmic reticulum.
  • A high-affinity pathway involves ryanodine receptor activation.
  • A low-affinity pathway involves inositol 1,4,5-trisphosphate (IP3) receptor activation.

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