Identification of the receptors for prolactin-releasing peptide (PrRP) and Carassius RFamide peptide (C-RFa) in chickens

Endocrinology. 2012 Apr;153(4):1861-74. doi: 10.1210/en.2011-1719. Epub 2012 Feb 21.


Prolactin-releasing peptide (PrRP) and its structurally related peptide, Carassius Arg-Phe-amide peptide (C-RFa), have been reported to play similar roles in regulating food intake and pituitary functions in vertebrates. However, the identity, functionality, and expression of the receptor(s) for PrRP and C-RFa remain largely unknown in nonmammalian vertebrates, including birds. In this study, three receptors homologous to mammalian PrRP receptor (PrRPR), named cPrRPR1, cPrRPR2, and cC-RFaR, respectively, were cloned from chicken brain by RT-PCR. Using a pGL3-NFAT-RE-luciferase reporter system, we demonstrated that cPrRPR1 and cPrRPR2 expressed in Chinese hamster ovarian cells could be activated by cPrRP₂₀ and cC-RFa₂₀ potently, whereas cC-RFaR could only be activated effectively by cC-RFa₂₀ (EC₅₀, 0.11 nM), indicating that cPrRPR1 and cPrRPR2 can function as common receptors for PrRP and C-RFa, whereas cC-RFaR is a receptor specific to C-RFa. Using a pGL3-CRE-luciferase reporter system, cPrRPR1, cPrRPR2, and cC-RFaR expressed in Chinese hamster ovarian cells were also shown to activate intracellular protein kinase A signaling pathway upon cC-RFa₂₀ treatment (100 nM). Moreover, RT-PCR assay revealed that cPrRPR1, cPrRPR2, and cC-RFaR were widely expressed in most adult chicken tissues examined, including various regions of brain. These findings, together with evidence of PrRP and C-RFa encoded by separate genes in chicken, Xenopus, and zebrafish, and the differential expression of PrRP and C-RFa genes in chicken tissues, strongly suggest that PrRP and C-RFa may play similar yet distinctive roles in nonmammalian vertebrates, including chicken, and their actions are mediated by common receptor(s) or a specific C-RFa receptor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • Chick Embryo
  • Chickens / metabolism*
  • Chromosome Mapping
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • DNA, Complementary / metabolism
  • Gene Expression Regulation
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism*
  • Rats
  • Receptors, Neuropeptide / genetics*
  • Receptors, Neuropeptide / metabolism*
  • Signal Transduction / physiology
  • Xenopus
  • Zebrafish


  • DNA, Complementary
  • Neuropeptides
  • RFamide peptide
  • Receptors, Neuropeptide
  • receptor, prolactin-releasing peptide
  • Cyclic AMP-Dependent Protein Kinases