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Rapid mobilization of Ca2+ from rat insulinoma microsomes by inositol-1,4,5-trisphosphate

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Abstract

Several hormones and neurotransmitters raise the cytosolic free Ca2+ concentration by stimulating the influx of Ca2+ and/or by mobilizing stored Ca2+ (refs 1,2). However, the link between the agonist receptor on the cell surface and the organelle(s) from which Ca2+ is mobilized is unknown. One feature of the agonists that increase cytosolic Ca2+ is their rapid induction of phosphatidylinositol turnover3–8 and polyphosphoinositide hydrolysis9–14; in some tissues this leads, within seconds, to a marked accumulation of the water-soluble products, inositol 1,4-bisphosphate (Ins1,4P2) and inositol-1,4,5-trisphosphate (Ins1,4,5P3)15–18, suggesting that these might mediate Ca2+ mobilization from internal pools17,18. Such an action of Ins1,4,5P3 has recently been inferred from studies with permeabilized pancreatic acinar cells19 and hepatocytes20,21. Here we show directly that Ins1,4,5P3 rapidly releases Ca2+ from a microsomal fraction of rat insulinoma but not from mitochondria or secretory granules. Moreover, this response is transient and desensitizes the microsomes to subsequent Ins1,4,5P3 additions. These results suggest that Ins1,4,5P3 functions as a cellular messenger inducing early mobilization of Ca2+ from the endoplasmic reticulum.

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Authors and Affiliations

  1. Institut de Biochimie Clinique, University of Geneva, Sentier de la Roseraie, 1211, Geneva, 4, Switzerland

    M. Prentki, T. J. Biden, D. Janjic & C. B. Wollheim

  2. Department of Biochemistry, AFRC Institute of Animal Physiology, Babraham, Cambridge, CB2 4AT, UK

    R. F. Irvine

  3. AFRC Unit of Insect Neurophysiology and Pharmacology, Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, UK

    M. J. Berridge

Authors
  1. M. Prentki
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  2. T. J. Biden
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  3. D. Janjic
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  4. R. F. Irvine
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  5. M. J. Berridge
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  6. C. B. Wollheim
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Prentki, M., Biden, T., Janjic, D. et al. Rapid mobilization of Ca2+ from rat insulinoma microsomes by inositol-1,4,5-trisphosphate. Nature 309, 562–564 (1984). https://doi.org/10.1038/309562a0

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  • DOI: https://doi.org/10.1038/309562a0

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