In subject area: Medicine and Dentistry
RFamide-related peptides (RFRPs) refer to a group of peptides characterized by the C-terminal amino acid sequence amide motif (LPXRFa), which includes variants such as RFRP-1, RFRP-2, and RFRP-3 in mammals. These peptides are involved in the inhibition of gonadotropin secretion and play a role in the regulation of the reproductive system.
AI generated definition based on: Steroids in the Laboratory and Clinical Practice, 2023
2019, Yen and Jaffe's Reproductive Endocrinology (Eighth Edition) Janet E. Hall
RFamide-related peptides (RFRPs) are the mammalian orthologues of gonadotropin inhibitory hormone (GnIH), which was first discovered in the hypothalamus of the quail. In the human, RFRP-1 and RFRP-3 neurons send axonal projections to GnRH neurons. RFRPs are secreted into the pituitary portal system, and their receptor, G protein–coupled receptor 147 (GPR147), is present on gonadotropes as well as in the hypothalamus. Taken together with functional data from animal and cellular systems, these findings suggest that RFRPs function at both the hypothalamus and pituitary to regulate the secretion of LH and FSH. Interestingly, there is also evidence that RFRPs increase food intake in sheep without reducing energy expenditure. There are currently limited data to address the role of these peptides in the human. A 3-hour infusion of custom-synthesized GnIH resulted in a modest suppression of LH secretion in postmenopausal women but failed to inhibit LH secretion in response to pulses of kisspeptin-10 in men. Additional studies will be required to ascertain the physiology and potential therapeutic role of RFRPs in men and women.
2018, Life Sciences Fahimeh Nourbakhsh, ... Ali Roohbakhsh
The RFamide peptides or RFamide-related peptides (RFRPs) family are a large family of neuropeptides that are characterized by the possession of an Arg-Phe-NH 2 motif at C-terminal extremities that is functionally critical. These peptides comprise neuropeptides FF (NPFF) and AF (NPAF), neuropeptides SF (NPSF or RFRP-1) and VF (NPVF or RFRP-3), prolactin-releasing peptide, and Kisspeptin.
Neuropeptide NPFF, which is also recognized as a morphine-modulating peptide, was isolated from bovine brain in 1985 for the first time. It is expressed ubiquitously in the CNS and has the highest expression in the hypothalamus, medulla, posterior pituitary, and the dorsal horn of the spinal cord, which are involved in pain control. NPFF is involved in pain perception via the activation of specific non-opioid receptors. The NPFF receptor family is part of the GPCRs superfamily called the RF-amide receptors. The receptors were originally identified as opioid-induced analgesia modulators and hyperalgesia inducers. It has been demonstrated to regulate pain mechanisms in different experimental models of inflammation and neuropathic pain. NPFF receptors are distinct from opioid receptors as NPFF does not bind to opioid receptors, but rather stimulates specific NPFF receptors. Two G i/o protein-coupled receptors have been discovered as NPFF cognate receptors namely NPFFR1 (GRP147) and NPFFR2 (GPR74). Both NPSF and NPVF are ligands for GRP147. However, GPR147 has a great affinity for NPFF. These orphan receptors have specific roles in NPFF-mediated actions as they are differently coupled to G proteins. NPFF receptors (GPR74 and GRP147) are expressed in many parts of the central nervous system. NPFFR2 has a unique expression in pain-processing regions such as the thalamus and dorsal raphe nucleus. NPFFR2 is also synthesized in the cell bodies of DRG neurons and is translocated to the nerve terminals of the afferent sensory neurons in the spinal dorsal horn. These receptors are expressed at high density in the dorsal horns of the spinal cord. In rodents, it was clearly shown that NPFFR1 is widely expressed in the brain tissue, while the NPFFR2 is expressed exclusively in the spinal cord. Based on the distribution pattern of these receptors, it seems that NPFFR2 mediates pain transmission in the spinal cord. Whereas NPFFR1 participates in neuroendocrine functions. The lack of spinal NPFFR1 proposes the hypothesis that the antinociceptive action of NPFF is mediated via NPFFR2 activation, while the NPFF pro-nociceptive effects are mediated via NPFFR1. In the human spinal cord, NPFFR1 expression has been observed as a notable exception to other mammalian species, suggesting that NPFFR2 has the same role in pain processing as NPFFR1. This exception suggests that in humans, both NPFFR1 and NPFFR2 has a role in pain processing.
The role of the NPFF-NPFFR system was primarily studied in nociception and opioid-induced analgesia. NPFF-NPFFR signaling caused either pain or analgesia depending on the route of administration or receptor type that was activated. Accordingly, the effect of NPFF and its analogs on pain has been reported with contradictory reports. In an experimental model of neuropathic pain, by unilateral ligation of two spinal nerves, administration of NPFF into the PAG significantly attenuated tactile allodynia. Moreover, in CFA-induced inflammation and unilateral sciatic nerve constriction models, i.t. and i.c.v. administration of NPFF dose-dependently attenuated the allodynia. In contrast, i.t. and i.c.v. injections of NPFF had no significant effects on thresholds to acute thermal or mechanical stimulation, which suggests the NPFF role in the modulation of chronic but not acute pain.
