A G protein-coupled receptor for UDP-glucose

Uridine 5'-diphosphoglucose (UDP-glucose) has a well established biochemica l role as a glycosyl donor in the enzymatic biosynthesis of carbohydrates. It is less well known that UDP-glucose may possess pharmacological activity , suggesting that a receptor for this molecule may exist, Here, we show tha t UDP-glucose, and some closely related molecules, potently activate the or phan G protein-coupled receptor KIAA0001 heterologously expressed in yeast or mammalian cells. Nucleotides known to activate P2Y receptors were inacti ve, indicating the distinctly novel pharmacology of this receptor. The rece ptor is expressed in a wide variety of human tissues, including many region s of the brain. These data suggest that some sugar-nucleotides may serve im portant physiological roles as extracellular signaling molecules in additio n to their familiar role in intermediary metabolism.