IP3mediated

IP3-mediated signaling refers to cellular processes initiated by inositol 1,4,5-trisphosphate (IP3), a second messenger produced when phospholipase C cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) in response to activated G protein-coupled receptors or receptor tyrosine kinases. IP3 diffuses through the cytosol and binds to IP3 receptors on the membranes of the endoplasmic reticulum, triggering release of calcium ions into the cytoplasm. The resulting rise in intracellular Ca2+ concentration acts as a versatile signal, regulating processes such as muscle contraction, neurotransmitter release, enzyme activity, and gene expression. Calcium signaling often occurs in concert with diacylglycerol (DAG), which remains in the membrane and activates protein kinase C, linking IP3-mediated Ca2+ release to additional downstream pathways.

IP3 receptors form intracellular Ca2+ channels (IP3R1, IP3R2, IP3R3) that are differentially expressed across tissues. Their activity is governed by IP3 binding, Ca2+ levels (which can both activate and inactivate the channel depending on concentration), and other modulators. Termination of IP3 signaling involves dephosphorylation and metabolism of IP3, reuptake of Ca2+ into the endoplasmic reticulum by SERCA pumps, and feedback mechanisms that limit receptor activity. Store-operated calcium entry, mediated by STIM and Orai proteins, often supplements IP3-mediated Ca2+ release by allowing extracellular Ca2+ influx to refill ER stores.

Physiological roles of IP3-mediated signaling are diverse, spanning secretion, cardiovascular function, neural activity, and metabolic regulation. Pharmacological agents that modulate IP3 receptors or the PLC–IP3–DAG axis are commonly used in research to dissect these pathways, though clinical applications remain limited and largely experimental.