Identification and characterization of two G protein-coupled receptors forneuropeptide FF

The central nervous system octapeptide, neuropeptide FF (NPFF), is believed to play a role in pain modulation and opiate tolerance. Two G protein-coup led receptors, NPFF1 and NPFF2, were isolated from human and rat central ne rvous system tissues. NPFF specifically bound to NPFF1 (K-d = 1.13 nm) and NPFF2 (K-d = 0.37 nm), and both receptors were activated by NPFF in a varie ty of heterologous expression systems. The localization of mRNA and binding sites of these receptors in the dorsal horn of the spinal cord, the latera l hypothalamus, the spinal trigeminal nuclei, and the thalamic nuclei suppo rts a role for NPFF in pain modulation. Among the receptors with the highes t amino acid sequence homology to NPFF1 and NPFF2 are members of the orexin , NPY, and cholecystokinin families, which have been implicated in feeding. These similarities together with the finding that BIBP3226, an anorexigeni c Y1 receptor ligand, also binds to NPFF1 suggest a potential role for NPFF 1 in feeding. The identification of NPFF1 and NPFF2 will help delineate the ir roles in these and other physiological functions.