Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (773 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: 1,4,5-IP3; Myo-Inositol 1,4,5-Trisphosphate; Myoinositol 1,4,5-Triphosphate; 1,4,5-InsP3; Inositol 1,4,5-Triphosphate.
Where it fits in the MeSH classification
- Broader topics
- Inositol Phosphates
Research landscape
PubMed indexes 6,677 records tagged with the MeSH heading “Inositol 1,4,5-Trisphosphate” (counts retrieved 2026-10-31). 134 of them (2.0%) were published from 2020 onward, and the busiest period so far is through 1999 with 4,282 records.
Reviews account for 518 records (7.8%) and meta-analyses for 1. Randomized controlled trials number 0 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 4,282 |
| 2000-2009 | 1,617 |
| 2010-2019 | 644 |
| 2020 onward | 134 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 518 | 7.8% |
| Meta-analyses | 1 | 0.0% |
| Randomized controlled trials | 0 | 0.0% |
Method: PubMed query "Inositol 1,4,5-Trisphosphate"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Inositol 1,4,5-trisphosphate receptors and their protein partners as signalling hubs | 2016 | Review article Design not recorded in structured metadata | 134 | cc by PMID 26830355 · DOI · PMC4887697 |
| Inositol 1,4,5-trisphosphate-induced Ca2+ signalling is involved in estradiol-induced breast cancer epithelial cell growth | 2010 | Research article Design not recorded in structured metadata | 73 | cc by PMID 20565939 · DOI · PMC2906470 |
| Conformational motions and ligand-binding underlying gating and regulation in IP3R channel | 2022 | Research article Design not recorded in structured metadata | 48 | cc by PMID 36376291 · DOI · PMC9663519 |
| Inside-Out IP3-Mediated G Protein-Coupled Receptor Activation Drives Intercellular Ca2+ Signaling in the Vascular Endothelium | 2025 | Research article Design not recorded in structured metadata | 7 | cc by PMID 40637265 · DOI · PMC12243451 |
Inositol 1,4,5-trisphosphate receptors and their protein partners as signalling hubs [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Inositol 1,4,5-trisphosphate receptors (IP3 Rs) are expressed in nearly all animal cells, where they mediate the release of Ca(2+) from intracellular stores.
- Closing excerpt
- We suggest that IP3 Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca(2+) signals.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (142 words)
Inositol 1,4,5-trisphosphate receptors (IP3 Rs) are expressed in nearly all animal cells, where they mediate the release of Ca(2+) from intracellular stores. The complex spatial and temporal organization of the ensuing intracellular Ca(2+) signals allows selective regulation of diverse physiological responses. Interactions of IP3 Rs with other proteins contribute to the specificity and speed of Ca(2+) signalling pathways, and to their capacity to integrate information from other signalling pathways. In this review, we provide a comprehensive survey of the proteins proposed to interact with IP3 Rs and the functional effects that these interactions produce. Interacting proteins can determine the activity of IP3 Rs, facilitate their regulation by multiple signalling pathways and direct the Ca(2+) that they release to specific targets. We suggest that IP3 Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca(2+) signals.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 26830355 · DOI · PMC4887697
Inositol 1,4,5-trisphosphate-induced Ca2+ signalling is involved in estradiol-induced breast cancer epithelial cell growth [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundCa2+ is a ubiquitous messenger that has been shown to be responsible for controlling numerous cellular processes including cell growth and cell death.
- Closing excerpt
- ConclusionsAltogether, our results are in favour of a role of IICS in MCF-7 cell growth, and we hypothesize that the regulation of IP3R3 expression by E2 is involved in this effect.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (280 words)
BackgroundCa2+ is a ubiquitous messenger that has been shown to be responsible for controlling numerous cellular processes including cell growth and cell death. Whereas the involvement of IP3-induced Ca2+ signalling (IICS) in the physiological activity of numerous cell types is well documented, the role of IICS in cancer cells is still largely unknown. Our purpose was to characterize the role of IICS in the control of growth of the estrogen-dependent human breast cancer epithelial cell line MCF-7 and its potential regulation by 17beta-estradiol (E2).ResultsOur results show that the IP3 receptor (IP3R) inhibitors caffeine, 2-APB and xestospongin C (XeC) inhibited the growth of MCF-7 stimulated by 5% foetal calf serum or 10 nM E2. Furthermore, Ca2+ imaging experiments showed that serum and E2 were able to trigger, in a Ca2+-free medium, an elevation of internal Ca2+ in a 2-APB and XeC-sensitive manner. Moreover, the phospholipase C (PLC) inhibitor U-73122 was able to prevent intracellular Ca2+ elevation in response to serum, whereas the inactive analogue U-73343 was ineffective. Western-blotting experiments revealed that the 3 types of IP3Rs are expressed in MCF-7 cells and that a 48 hours treatment with 10 nM E2 elevated IP3R3 protein expression level in an ICI-182,780 (a specific estrogen receptor antagonist)-dependent manner. Furthermore, IP3R3 silencing by the use of specific small interfering RNA was responsible for a drastic modification of the temporal feature of IICS, independently of a modification of the sensitivity of the Ca2+ release process and acted to counteract the proliferative effect of 10 nM E2.ConclusionsAltogether, our results are in favour of a role of IICS in MCF-7 cell growth, and we hypothesize that the regulation of IP3R3 expression by E2 is involved in this effect.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 20565939 · DOI · PMC2906470
Conformational motions and ligand-binding underlying gating and regulation in IP3R channel [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Inositol-1,4,5-trisphosphate receptors (IP3Rs) are activated by IP3 and Ca2+ and their gating is regulated by various intracellular messengers that finely tune the channel activity.
- Closing excerpt
- This work represents a stepping-stone to developing mechanistic understanding of conformational pathways underlying ligand-binding, activation and regulation of the channel.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (139 words)
Inositol-1,4,5-trisphosphate receptors (IP3Rs) are activated by IP3 and Ca2+ and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IP3R1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. Using a deep-learning approach and 3D variability analysis we extracted molecular motions of the key protein domains from cryo-EM density data. We find that IP3 binding relies upon intrinsic flexibility of the ARM2 domain in the tetrameric channel. Our results highlight a key role of dynamic side chains in regulating gating behavior of IP3R channels. This work represents a stepping-stone to developing mechanistic understanding of conformational pathways underlying ligand-binding, activation and regulation of the channel.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36376291 · DOI · PMC9663519
Inside-Out IP3-Mediated G Protein-Coupled Receptor Activation Drives Intercellular Ca2+ Signaling in the Vascular Endothelium [4]
Abstract reading summary — source excerpts
- Opening excerpt
- The endothelium's control of nearly all vascular function relies on rapid intercellular communication to coordinate cellular activity across scale.
- Closing excerpt
- Our findings uncover a previously unrecognized mechanism of endothelial communication, in which noncanonical IP3-driven transcellular activation of G protein-coupled receptors sustains a regenerative signaling loop, highlighting a novel framework for intercellular coordination in the vascular endothelium.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (212 words)
The endothelium's control of nearly all vascular function relies on rapid intercellular communication to coordinate cellular activity across scale. A key form of intercellular communication arises from the regenerative propagation of IP3-evoked Ca2+ signals from cell to cell, which regulate vessel tone, modulate vascular permeability, and determine immune responses. Despite their importance, the mechanisms by which regenerative propagation of IP3-evoked Ca2+ signals occurs are poorly understood. Here, in intact resistance arteries, precision photolysis of IP3 combined with high-resolution mesoscale imaging, targeted drug application, and advanced analytical techniques was used to determine the mechanisms underlying regenerative propagation of IP3-evoked Ca2+ signals in the endothelium. Elevated IP3 in the initiating cell triggers a noncanonical inside-out signaling mechanism that leads to transcellular activation of a Gαq/11-coupled receptor in a neighboring (receiving) cell. This, in turn, initiates canonical outside-in signaling via PLC, leading to the hydrolysis of PIP2 and production of IP3. This process creates a regenerative, IP3-dependent signaling cascade operating between adjacent cells. Notably, neither Ca2+ nor IP3 diffusion through gap junctions plays a significant role in intercellular communication. Our findings uncover a previously unrecognized mechanism of endothelial communication, in which noncanonical IP3-driven transcellular activation of G protein-coupled receptors sustains a regenerative signaling loop, highlighting a novel framework for intercellular coordination in the vascular endothelium.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40637265 · DOI · PMC12243451
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Inositol trisphosphate and calcium signalling [5]
- Research article Capacitative calcium entry revisited [6]
- Research article 2-aminoethoxydiphenyl borate (2-APB) is a reliable blocker of store-operated Ca2+ entry but an inconsistent inhibitor of InsP3-induced Ca2+ release [7]
- Research article The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease [8]
- Research article Inositol trisphosphate and calcium signalling mechanisms [9]
- Research article The pharmacology of intracellular Ca(2+)-release channels [10]
References
- Prole DL, Taylor CW. Inositol 1,4,5-trisphosphate receptors and their protein partners as signalling hubs. . 2016. PMID 26830355 · DOI · PMC4887697
- Szatkowski C, Parys JB, Ouadid-Ahidouch H, Matifat F. Inositol 1,4,5-trisphosphate-induced Ca2+ signalling is involved in estradiol-induced breast cancer epithelial cell growth. . 2010. PMID 20565939 · DOI · PMC2906470
- Fan G, Baker MR, Terry LE, Arige V, Chen M, Seryshev AB, et al.. Conformational motions and ligand-binding underlying gating and regulation in IP3R channel. . 2022. PMID 36376291 · DOI · PMC9663519
- Buckley C, Zhang X, Lee MD, Wilson C, McCarron JG. Inside-Out IP3-Mediated G Protein-Coupled Receptor Activation Drives Intercellular Ca2+ Signaling in the Vascular Endothelium. . 2025. PMID 40637265 · DOI · PMC12243451
- Berridge MJ. Inositol trisphosphate and calcium signalling. Nature. 1993. PMID 8381210 · DOI
- Putney JW. Capacitative calcium entry revisited. Cell Calcium. 1990. PMID 1965707 · DOI
- Bootman MD, Collins TJ, Mackenzie L, Roderick HL, Berridge MJ, Peppiatt CM. 2-aminoethoxydiphenyl borate (2-APB) is a reliable blocker of store-operated Ca2+ entry but an inconsistent inhibitor of InsP3-induced Ca2+ release. FASEB J. 2002. PMID 12153982 · DOI
- Berridge MJ. The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease. Physiol Rev. 2016. PMID 27512009 · DOI
- Berridge MJ. Inositol trisphosphate and calcium signalling mechanisms. Biochim Biophys Acta. 2009. PMID 19010359 · DOI
- Ehrlich BE, Kaftan E, Bezprozvannaya S, Bezprozvanny I. The pharmacology of intracellular Ca(2+)-release channels. Trends Pharmacol Sci. 1994. PMID 7754532 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.