Neuropeptide FF receptor, type 1 (IPR005396)

Short name: NPFF_rcpt_1

Overlapping homologous superfamilies


Family relationships


Neuropeptide FF receptors [PMID: 10837915] belong to a family of neuropeptides containing an RF-amide motif at their C terminus which have a high affinity for the pain modulatory peptide neuropeptide NPFF (NPFF) [PMID: 10851242]. Neuropeptide FF (NPFF) receptors have two subtypes, neuropeptide FF receptor type 1 (NPFF1) and neuropeptide FF receptor type 2 (NPFF2), they are members of rhodopsin G protein-coupled receptor family. The neuropeptide FF is found at high concentrations in the posterior pituitary, spinal cord, hypothalamus and medulla and is believed to be involved in pain modulation, opioid tolerance, cardiovascular regulation, memory and neuroendocrine regulation [PMID: 8804117, PMID: 9593588, PMID: 10612711, PMID: 20803521].

Comparing the distribution of NPFF1 and NPFF2 receptors in different species reveals important species differences [PMID: 14696013]. The NPFF1 receptor is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus, is thought to participate in neuroendocrine functions. Whereas as the NPFF2 receptor is present in high density, particularly in mammals in the superficial layers of the spinal cord [PMID: 16443306] where it is involved in nociception and modulation of opioid functions [PMID: 17224450], consistent with a potential role of NPFF in the modulation of sensory inputs, like pain responses [PMID: 17854890, PMID: 18804517, PMID: 18823989].

This entry represents NPFF1 receptor, which is expressed at highest levels in the hypothalamus, with moderate expression in the thalamus, midbrain, medulla oblongata, testis and eye [PMID: 11025660]. NPFF1 receptor has been found to regulate adenylyl cyclase in some recombinant cell lines [PMID: 11025660, PMID: 11481330]. It also couples with Gi protein to inhibit adenylyl cyclase (AC) [PMID: 11025660], and reduces the activities of cAMP-dependent protein kinase (PKA) and mitogen-activated protein kinase (MAPK) signaling cascade.

GO terms

Biological Process

GO:0007186 G protein-coupled receptor signaling pathway

Molecular Function

GO:0008188 neuropeptide receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.