The two mammalian neuropeptides NPFF and NPAF have been shown to have important roles in nociception, anxiety, learning and memory, and cardiovascular reflex. Two receptors (FF1 and FF2) have been molecularly identified for NPFF and NPAF. We have now characterized a novel gene designated NPVF that encodes two neuropeptides highly similar to NPFF. NPVF mRNA was detected specifically in a region between the dorsomedial and ventromedial hypothalamic nuclei. NPVF-derived peptides displayed higher affinity for FF1 than NPFF-derived peptides, but showed poor agonist activity for FF2. Following intracerebral ventricular administration, a NPVF-derived peptide blocked morphine-induced analgesia more potently than NPFF in both acute and inflammatory models of pain. In situ hybridization analysis revealed distinct expression patterns of FF1 and FF2 in the rat central nervous system. FF1 was broadly distributed, with the highest levels found in specific regions of the limbic system and the brainstem where NPVF-producing neurons were shown to project. FF2, in contrast, was mostly expressed in the spinal cord and some regions of the thalamus. These results indicate that the endogenous ligands for FF1 and FF2 are NPVF- and NPFF-derived peptides, respectively, and suggest that the NPVF/FF1 system may be an important part of endogenous anti-opioid mechanism.
Liu Q, et al. J Biol Chem. 2001 Oct 5;276(40):36961-9. Epub 2001 Jul 31.
A.) predicted polypeptide sequence of human NPVF. The signal peptide sequence (S.P.) is underlined. The two potential mature peptides, NPSF-(1–37) and NPVF, are boxed.
B.) alignment of the polypeptide sequences of the NPVF precursors of human, bovine, mouse, rat, and quail. The predicted signal peptide sequence (S.P.), NPSF, and NPVF are underlined. The peptides predicted only in the quail precursor areunderlined with dashed line. The GenBank™ accession numbers are as follows: human NPVF, AF330057; mouse NPVF, AF330058; rat NPVF, AF330059; bovine NPVF, AB040291; chicken GnIH, AB039815.
