G protein-coupled receptor-mediated calcium signaling pathway (GPCR-Ca2+ signaling)

G protein-coupled receptor (GPCR)-mediated calcium signaling is a fundamental mechanism by which cells respond to external stimuli such as hormones and neurotransmitters (StatPearls, 2023). This pathway typically involves the activation of Gq-type heterotrimeric G proteins, which in turn stimulate the enzyme phospholipase C (PLC) (Nature, 2020). PLC catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into two second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) (UniProt). IP3 diffuses through the cytosol to bind to IP3 receptors on the endoplasmic reticulum, causing a rapid release of stored calcium ions into the cytoplasm (PubMed, 2012). This increase in intracellular calcium regulates a wide array of physiological processes, including muscle contraction, neurotransmitter release, and gene transcription (NIH). Dysregulation of this pathway is implicated in numerous pathologies, including hypertension, heart failure, and various cancers (NCBI, 2014). Consequently, the individual receptors and enzymes within this pathway are frequent targets for pharmacological intervention, such as angiotensin II receptor blockers and muscarinic agonists (PubChem).

Other names

GPCR-mediated calcium signalingGq protein-coupled signalingPhosphoinositide signaling pathwayCalcium-mediated signal transduction

Activation of Gq-coupled receptors leads to Phospholipase C (PLC) activation, which hydrolyzes PIP2 into IP3 and DAG. IP3 then binds to receptors on the endoplasmic reticulum to trigger the release of intracellular calcium ions.