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Cell Mol Life Sci. 2011 Jan;68(1):85-95. doi: 10.1007/s00018-010-0517-1. Epub 2010 Sep 2.

GPR39: a Zn(2+)-activated G protein-coupled receptor that regulates pancreatic, gastrointestinal and neuronal functions.

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School of Medicine, University of St Andrews, Medical and Biological Sciences Building, St Andrews, Fife, KY16 9TF, UK.


GPR39 is a vertebrate G protein-coupled receptor related to the ghrelin/neurotensin receptor subfamily. The receptor is expressed in a range of tissues including the pancreas, gut/gastrointestinal tract, liver, kidney and in some regions of the brain. GPR39 was initially thought to be the cognitive receptor for the peptide hormone, obestatin. However, subsequent in vitro studies have failed to demonstrate binding of this peptide to the receptor. Zn(2+) has been shown to be a potent stimulator of GPR39 activity via the Gα(q), Gα(12/13) and Gα(s) pathways. The potency and specificity of Zn(2+) in activating GPR39 suggest it to be a physiologically important agonist. GPR39 is now emerging as an important transducer of autocrine and paracrine Zn(2+) signals, impacting upon cellular processes such as insulin secretion, gastric emptying, neurotransmission and epithelial repair. This review focuses on the molecular, structural and biological properties of GPR39 and its various physiological functions.

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