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Point-mutation studies have revealed that changes in amino acid sequence may alter binding of NmU to its receptors, NMUR1 and NMUR2; for example, substitution of certain residues may not affect NmU activity at NMUR2, but reduces the response mediated by NMUR1 (13).
Moreover, NmS binds to NmU receptors NMUR1 and NMUR2, with some data suggesting that NMUR2 has higher affinity for NmS than for NmU (16).
Two different receptors exist for NmU, termed NMUR1 (also known as GPR66 and FM-3) and NMUR2 (also known as TGR-1 and FM-4), encoded by genes located in human chromosomes 2 and 5, respectively (14, 28, 29, 35-39).
Most studies agree that NMUR1 is preferentially expressed in the periphery, particularly in the gastrointestinal tract, while NMUR2 is predominantly expressed in the central nervous system (41).
It should be noted that NmU has also been shown to act independently of NMUR1 and NMUR2.
NmU binding to NMUR1 and NMUR2 results in increased intracellular [Ca.
Mice deficient in NMUR2 do not display differences in their response to stress compared to wild-type mice, suggesting that this receptor does not mediate NmU effects on the stress response (66).
However, mice deficient in NMUR2 do not reproduce the phenotype of [NmU.
Furthermore, NmU treatment induced ERK activation and progesterone release mediated by NMUR2 in cultured theca/interstitial cells of the ovary (107).
M2 EQUITYBITES-February 22, 2012-Omeros Corporation wins USD1m NIDA grant for non addicting NMUR2 drug development programme(C)2012 M2 COMMUNICATIONS http://www.
This NIDA grant will be used to fund medicinal chemistry for proprietary compounds that interact with NMUR2 and the company will retain ownership of any compounds developed from the grant.
According to the company, NMUR2 is a non-orphan G protein-coupled receptor (GPCR) linked to pain.
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