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# IP₃, DAG and calcium pathway

Some hormones activate phospholipase C: IP₃ releases calcium from the reticulum and DAG activates protein kinase C.

Updated 2026-11-01

## Key facts

- Gαq activates phospholipase C-β, which splits membrane PIP₂ into IP₃ (soluble) and diacylglycerol (DAG, stays in the membrane).
- IP₃ opens its receptor-channel on the endoplasmic reticulum and Ca²⁺ flows into the cytosol.
- DAG and Ca²⁺ activate protein kinase C (PKC); Ca²⁺ with calmodulin activates other kinases.
- Gq receptors: α1-adrenergic, vasopressin V1, angiotensin II AT1, muscarinic M1 and M3, histamine H1, and those for oxytocin, TRH and GnRH.

## In detail

- The signal starts as in the cAMP pathway: the hormone activates the receptor and the Gαq subunit takes up GTP.
- Phospholipase C-β hydrolyses phosphatidylinositol 4,5-bisphosphate (PIP₂): it releases inositol 1,4,5-trisphosphate (IP₃) and leaves DAG in the membrane.
- IP₃ diffuses to the endoplasmic reticulum and opens the IP₃ receptor; cytosolic Ca²⁺ rises about a hundredfold within seconds.
- Ca²⁺ binds calmodulin; the complex activates myosin light-chain kinase (smooth muscle contraction), CaM kinases and phosphorylase kinase (glycogen breakdown).
- PKC, activated by DAG and Ca²⁺, phosphorylates growth and secretion proteins. DAG can also release arachidonic acid for eicosanoids.
- The signal ends when SERCA (reticulum) and PMCA (membrane) pumps return the Ca²⁺, and IP₃ is dephosphorylated to inositol, which is recycled into PIP₂.

**Also called**
Phospholipase C pathway, Gq pathway

## Clinical notes

- Lithium inhibits inositol monophosphatase and reduces inositol recycling; this is one explanation for its effect in bipolar disorder.
- α1 agonists (vasoconstriction) and α1 blockers (antihypertensives, prostatic hyperplasia) act on this pathway.
- Phorbol esters, experimental tumour promoters, mimic DAG and keep PKC switched on.
- In the liver, adrenaline through α1 and vasopressin raise Ca²⁺ and activate phosphorylase kinase even when cAMP does not change.

## Related conditions

- [Arterial hypertension](https://durgical.com/en/conditions/arterial-hypertension/)
- [Asthma](https://durgical.com/en/conditions/asthma/)

## Related

- [G protein-coupled receptors and cAMP](https://durgical.com/en/biochemistry/topics/g-protein-coupled-receptors-and-camp/)
- [Glycogen phosphorylase](https://durgical.com/en/biochemistry/enzymes/glycogen-phosphorylase/)
- [Adrenaline](https://durgical.com/en/biochemistry/molecules/adrenaline/)
- [Eicosanoids: prostaglandins, thromboxanes and leukotrienes](https://durgical.com/en/biochemistry/topics/eicosanoids-prostaglandins-thromboxanes-and-leukotrienes/)
- [Receptor tyrosine kinases](https://durgical.com/en/biochemistry/topics/receptor-tyrosine-kinases/)
- [Hormone classes and mechanisms](https://durgical.com/en/biochemistry/topics/hormone-classes-and-mechanisms/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which two second messengers does phospholipase C make from PIP₂?

Inositol trisphosphate (IP₃), which releases Ca²⁺ from the reticulum, and diacylglycerol (DAG), which activates PKC.

## How does an α1 agonist make smooth muscle contract?

Through Gq, IP₃ rises, Ca²⁺ is released, calmodulin activates myosin light-chain kinase and myosin is phosphorylated.

## Which enzyme of this pathway does lithium inhibit?

Inositol monophosphatase, which limits inositol recycling to make new PIP₂.

## Which pumps clear Ca²⁺ from the cytosol at the end of the signal?

SERCA, which returns it to the reticulum, and PMCA, which pumps it out of the cell.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [GNAS: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (human)](https://www.uniprot.org/uniprotkb/P63092/entry) (UniProt, 2026); [Hormones | Hormone Function | MedlinePlus](https://medlineplus.gov/hormones.html) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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