Inositol second messenger system

The Inositol second messenger system refers to a signal transduction pathway wherein extracellular ligands (such as hormones and neurotransmitters) activate membrane receptors—most commonly G protein-coupled receptors—which in turn activate phospholipase C. This enzyme hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate two intracellular messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 diffuses through the cytoplasm and binds to its receptor on the endoplasmic reticulum, triggering calcium ion release into the cytosol, which then activates various downstream processes including muscle contraction, secretion, metabolism, and changes in gene expression. DAG remains in the membrane and activates protein kinase C, further propagating the signal. The system plays a central role in cellular signaling and physiological regulation across many cell types, and is indirectly involved in a broad spectrum of diseases owing to its regulation of calcium and kinase signaling. The system itself is not a drug target, but its individual molecules (e.g., the IP3 receptor) are pharmacologically targetable.

Other names

Phosphoinositol signaling pathwayIP3 signaling pathwayinositol lipid signaling

For pathway components (e.g., IP3 receptor antagonists), mechanisms include inhibition of Ca2+ release from ER; PLC inhibitors prevent IP3/DAG formation