The Second Messenger Linking Receptor Activation to Internal Ca Release in Liver
Abstract
The increase in cytosolic [Ca2+] induced by Ca-mobilizing hormones in liver is mainly due to release of Ca from intracellular stores. For Ca to be released from internal sites a messenger must be formed at the plasma membrane which diffuses into the cytosol to signal Ca release from the intracellular organelles. One of the first actions of these hormones is to cause breakdown of the polyphosphoinositides to form soluble inositol phosphates. Some evidence for the idea that these substances could be the second messenger has been obtained in pancreatic acinar cells. Here we have found that hormone activation of hepatocytes causes rapid breakdown of phosphatidylinositol 4,5-bisphosphate [ PtdIns (4,5)P2] to form inositol trisphosphate ( InsP3 ). When applied to permeabilized hepatocytes, InsP3 releases Ca from non-mitochondrial ATP-dependent pools. This suggests that InsP3 could be the messenger linking Ca-mobilizing receptor activation to intracellular Ca release in liver.
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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 [3]
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A model for receptor-regulated calcium entry
Putney, J. W. (1986) · Cell Calcium · doi:10.1016/0143-4160(86)90026-6 · Cited by 2,575 · see citing works
Self-citationEssential fatty acids and the skin
WRIGHT, S. (1991) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1991.tb14786.x · Cited by 78 · see citing works
From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease
Mishra, S. H., Chatterjee, S., Viera-Preval, L., & Guha, P. (2025) · Biomolecules · doi:10.3390/biom15091266 · Cited by 1 · see citing works
“Since Michael Berridge and colleagues’ seminal discovery in 1983 [2] that InsP3 mobilizes intracellular calcium release from the endoplasmic reticulum [1–3], extensive research has illuminated InsP3’s crucial roles in regulating diverse physiological processes.”
- Authors
- Burgess, G. M., Godfrey, P. P., McKinney, J. S., Berridge, M. J., Irvine, R. F., & Putney, J. W.
- Affiliations
- Virginia Commonwealth University Medical Center (US)
- University of Cambridge (GB)
- ORCID
- Putney, James W.
- Venue
- Nature
- Published
- 1984-05
- Volume
- 309
- Issue
- 5963
- Pages
- 63-66
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1994924034
- Cited by
- 554
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 1 · 2018: 2 · 2017: 7 · 2016: 1 · 2015: 4 · 2014: 8 · 2013: 1 · 2012: 3
- FWCI
- 46.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- inositol trisphosphate, second messengers, intracellular calcium release, phosphatidylinositol 4,5-bisphosphate, phospholipase C, hepatocytes, intracellular calcium stores, liver, receptor activation
- MeSH terms
- Animals, Calcium, Cell Membrane, Guinea Pigs, Inositol, Inositol Phosphates, Kinetics, Liver, Male, Receptors, Adrenergic, alpha, Saponins, Sugar Phosphates, Tritium, Inositol 1,4,5-Trisphosphate, In Vitro Techniques
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