Microinjection of 26RFa, an endogenous ligand for the glutamine RF-amide peptide receptor (QRFP receptor), into the rostral ventromedial medulla (RVM), locus coelureus (LC), and periaqueductal grey (PAG) produces an analgesic effect in rats

An excitatory lateral hypothalamic circuit orchestrating pain behaviors in mice

“…LH PV neuronal activity was also altered during formalin-induced inflammation. Formalin injection, which causes discrete phases of acute and inflammatory forms of pain behavior, into the hindpaw contralateral to the imaged LH hemisphere evoked increases in calcium transient frequencies that were more pronounced than those observed during injection of the paw ipsilateral to the imaged LH hemisphere, likely reflecting decussation of the nociceptive signal at the spinal level ( Dafny et al, 1996 ; Yoshida et al, 2019 ; Yamada et al, 2012 ). It is worthwhile to note the advantages of using a single-photon miniscope, which enables single-cell resolution of neuronal activity.…”

Point-Substitution of Phenylalanine Residues of 26RFa Neuropeptide: A Structure-Activity Relationship Study

“…In humans, both 26RFa-and 43RFa-immunoreactive forms have been detected in hypothalamic and spinal cord extracts [9]. Interestingly, the presence of a tribasic cleavage site (Arg-Lys-Arg/Lys) within the 26RFa sequence suggests that the C-terminal heptapeptide GGFSFRF-NH 2 , named 26RFa (20)(21)(22)(23)(24)(25)(26) , could also be produced from the precursor. However, to date, this fragment, whose sequence is highly conserved in tetrapods, has not been identified as a mature product of the 26RFa/QRFP gene transcription.…”

“…named 26RFa (20)(21)(22)(23)(24)(25)(26), could also be produced from the precursor. However, to date, this fragment, whose sequence is highly conserved in tetrapods, has not been identified as a mature product of the 26RFa/QRFP gene transcription.…”

“…In contrast, the residues of the -Phe 24 -Arg 25 -Phe 26 -NH2 triad are very sensitive to substitutions and only tolerate subtle amendments for improving bioactivity like the ω-methylation of arginine 25 [38]. To date, few replacements have been reported in the phenylalanine positions of 26RFa (20)(21)(22)(23)(24)(25)(26) [5]. As previously suggested for PrRP and kisspeptin [40], our work emphasizes that optimized modifications in the C-terminal part of 26RFa are mandatory to design selective and potent peptidergic ligands for hQRFPR.…”

“…However, 26RFa can be downsized from the N-terminal extremity with a gradual decrease in its ability to mobilize intracellular calcium concentration ([Ca 2+ ] i ) in CHO cells transfected by the human QRFPR (hQRFPR) [36]. Since 26RFa (20)(21)(22)(23)(24)(25)(26) (LV-2021) mimics the orexigenic and gonadotropic effects of full-length 26RFa [12,17], it appears that this C-terminal heptapeptide can serve as a molecular scaffold for designing low molecular weight, potent and stable hQRFPR ligands. As a matter of fact, 26RFa (20)(21)(22)(23)(24)(25)(26) has already been successfully used to design nanomolar active agonists such as [Nva 23 ]26RFa (20)(21)(22)(23)(24)(25)(26) (LV-2073) [36], [Cmpi 21 , aza-β 3 -Hht 23 ]26RFa (21)(22)(23)(24)(25)(26) (LV-2172) [37], and [(Me) ω Arg 25 ]26RFa (20)(21)(22)(23)(24)(25)(26) (LV-2186) [38], as well as proteolytic resistant pseudopeptides (Figure 2) [39].…”