Biochemistry · Topic
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
Related
- G protein-coupled receptors and cAMP
- Glycogen phosphorylase
- Adrenaline
- Eicosanoids: prostaglandins, thromboxanes and leukotrienes
- Receptor tyrosine kinases
- 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.
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) (UniProt, 2026); Hormones | Hormone Function | MedlinePlus (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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Representative model, for educational purposes only.