Neuropeptide FF 1 Receptor (NPFF1 or hFF1) and Neuropeptide FF 2 Receptor (NPFF2) belong to the G protein-coupled receptor 1 family. Both NPFF1 and NPFF2 are integral membrane proteins that act as receptors for NPAF (A-18- F-amide) and NPFF (F-8-F-amide) neuropeptides. Both NPFF proteins may be activated by synthetic or naturally occurring FMRF-amide-like ligands. The receptors are mediated by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. NPFF1 Receptors is highly expressed in the human hypothalamus and amygdala, indicating a possible role for NPFF1 in central autonomic and neuroendocrine control in the human brain. Based in part on NPFF2 Receptor expression in diencephalon and superficial layers of the spinal cord, NPFF2 Receptor is thought to be involved in the modulation of sensory input and opioid analgesia.