Relaxin family peptide receptor 3 (RXFP3)

Relaxin family peptide receptor 3 (RXFP3) is a class A, rhodopsin-like G protein-coupled receptor (GPCR) that serves as the primary cognate receptor for the neuropeptide relaxin-3 (also known as insulin-like peptide 7, INSL7). RXFP3 is predominantly expressed in the central nervous system, particularly within limbic and hypothalamic circuits, and is involved in modulation of arousal, stress response, feeding, metabolism, neuroendocrine regulation, and memory formation. Activation of RXFP3 by relaxin-3 results in inhibition of cAMP signaling through Gαi coupling, and can also activate MAP kinase pathways. RXFP3 is being actively explored as a therapeutic target for neuropsychiatric and neurodegenerative conditions due to its role in stress, cognition, and behavioral modulation.

Other names

RXFP3GPCR135SALPR (somatostatin- and angiotensin-like peptide receptor)Relaxin-3 receptor

Agonists: Bind to RXFP3 and primarily couple to Gαi proteins, leading to inhibition of cAMP production (via pertussis toxin-sensitive mechanism). Also activates MAPK pathways including p38MAPK, JNK1/2, and ERK1/2. Experimental antagonists: Block these pathways and the downstream central effects on stress, feeding, etc.