Cited by 1,954Protein Kinase Regulation and GTPase SignalingLipid metabolism and biosynthesisCellular transport and secretion

Changes in the Levels of Inositol Phosphates after Agonist-Dependent Hydrolysis of Membrane Phosphoinositides

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Berridge, M J, Dawson, R M C, Downes, C P, Heslop, J P, Irvine, R F·1983·Biochemical Journal

Abstract

The formation of inositol phosphates in response to agonists was studied in brain slices, parotid gland fragments and in the insect salivary gland. The tissues were first incubated with [3H]inositol, which was incorporated into the phosphoinositides. All the tissues were found to contain glycerophosphoinositol, inositol 1-phosphate, inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate, which were identified by using anion-exchange and high-resolution anion-exchange chromatography, high-voltage paper ionophoresis and paper chromatography. There was no evidence for the existence of inositol 1:2-cyclic phosphate. A simple anion-exchange chromatographic method was developed for separating these inositol phosphates for quantitative analysis. Stimulation caused no change in the levels of glycerophosphoinositol in any of the tissues. The most prominent change concerned inositol 1,4-bisphosphate, which increased enormously in the insect salivary gland and parotid gland after stimulation with 5-hydroxytryptamine and carbachol respectively. Carbachol also induced a large increase in the level of inositol 1,4,5-trisphosphate in the parotid. Stimulation of brain slices with carbachol induced modest increase in the bis- and tris-phosphate. In all the tissues studied, there was a significant agonist-dependent increase in the level of inositol 1-phosphate. The latter may be derived from inositol 1,4-bisphosphate, because homogenates of the insect salivary gland contain a bisphosphatase in addition to a trisphosphatase. These results suggest that the earliest event in the stimulus-response pathway is the hydrolysis of polyphosphoinositides by a phosphodiesterase to yield inositol 1,4,5-trisphosphate and inositol 1,4-bisphosphate, which are subsequently hydrolysed to inositol 1-phosphate and inositol. The absence of inositol 1:2-cyclic phosphate could indicate that, at very short times after stimulation, phosphatidylinositol is not catabolized by its specific phosphodiesterase, or that any cyclic derivative liberated is rapidly hydrolysed by inositol 1:2-cyclic phosphate 2-phosphohydrolase.

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  • InsP3 mobilizes intracellular calcium release from the endoplasmic reticulum.

    “Since Michael Berridge and colleagues’ seminal discovery in 1983 [2] that InsP3 mobilizes intracellular calcium release from the endoplasmic reticulum [1,2,3], extensive research has illuminated InsP3’s crucial roles in regulating diverse physiological processes.”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [2]

    The Abstract and Discussion report that calcium-signalling agonists stimulate phosphoinositide hydrolysis and production of Ins(1,4,5)P3. They do not state that InsP3 itself releases calcium from the endoplasmic reticulum. Searches for intracellular calcium release and the endoplasmic reticulum found no passage establishing that attributed discovery. (LLM, conf=0.77)

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References 21 · Cited by 1,954

Research works printed but not linked: 4

  1. Downes, C. P. & Michell, R. H. (1982) Cell Calcium in the press
  2. Irvine, R. F., Dawson, R. M. C. & Freinkel, N. (1982) Contemporary Metabolism (Freinkel, N., ed.), vol. 2, pp. 301-302, Plenum Press, New York
  3. Kirk, C. J., Creba, J. A., Downes, C. P. & Michell, R. H. (198 1) Biochem. Soc. Trans. 9, 377-379
  4. Michell, R. H., Kirk, C. J., Jones, L. M., Downes, C. P. & Creba, J. A. (1981) Philos. Trans. R. Soc. London Ser. B 296, 123-137

Authors
Berridge, M. J., Dawson, R. M. C., Downes, C. P., Heslop, J. P., & Irvine, R. F.
Affiliations
University of Cambridge (GB)
Venue
Biochemical Journal
Published
1983-05-15
Volume
212
Issue
2
Pages
473-482
ISSN
0306-3283 (ISSN-L)
OpenAlex
W1802980406
Cited by
1,954
References
21
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 1 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 8 · 2014: 11 · 2013: 9 · 2012: 7
FWCI
46.78
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
inositol phosphates, phosphoinositide hydrolysis, inositol 1,4,5-trisphosphate, inositol 1,4-bisphosphate, inositol-1-phosphate, phosphodiesterase, phosphatidylinositol, serotonin, carbachol, salivary glands, parotid gland, brain slices, agonist stimulation, signal transduction
MeSH terms
Animals, Autonomic Agents, Brain, Cell Membrane, Chromatography, Ion Exchange, Diptera, Hydrolysis, Inositol Phosphates, Parotid Gland, Phosphatidylinositols, Salivary Glands, Sugar Phosphates, Rats, In Vitro Techniques

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