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Research ArticleNEUROPHARMACOLOGY

Prolactin Releasing Peptide Has High Affinity and Efficacy at Neuropeptide FF2 Receptors

Mia Engström, Annika Brandt, Siegfried Wurster, Juha-Matti Savola and Pertti Panula
Journal of Pharmacology and Experimental Therapeutics June 2003, 305 (3) 825-832; DOI: https://doi.org/10.1124/jpet.102.047118
Mia Engström
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Annika Brandt
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Siegfried Wurster
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Juha-Matti Savola
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Pertti Panula
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Abstract

Neuropeptide FF (NPFF) and prolactin-releasing peptide (PrRP) are two members of the RFamide peptide family. In this study we investigated whether these RFamide peptides, which have common structural features in their C-terminal RFamide motif and share several physiologically important functions, could exert their effects through the same set of receptors. The affinity and functional activity of several related RFamide peptides were determined at the human neuropeptide FF receptor subtype 2 (hNPFF2) and the human prolactin-releasing peptide (hPrRP) receptors. The full-length human prolactin releasing peptide 31 (hPrRP31) had significantly higher efficacy compared with NPFF and its stable analog, (1DMe)Y8Fa, at the hNPFF2 receptor. In contrast, NPFF and (1DMe)Y8Fa were not efficacious at the hPrRP receptor. Our study indicated a generally relatively low level of discrimination for RFamide peptides at the NPFF receptor, whereas the hPrRP receptor clearly preferred PrRP or very closely related peptides. The seemingly promiscuous binding of the RFamide peptides to the NPFF receptor was further confirmed by receptor autoradiography. PrRP may thus signal through the NPFF receptors in vivo.

Footnotes

  • Financial support was received from the Technology Development Fund (TEKES) and the Academy of Finland.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • DOI: 10.1124/jpet.102.047118.

  • ABBREVIATIONS: NPFF, neuropeptide FF; PrRP, prolactin-releasing peptide; RFRP, RFamide-related peptide; hNPFF2, human neuropeptide FF receptor subtype 2; CHO, Chinese hamster ovary; NPY, neuropeptide Y; GPCR, G protein-coupled receptor; [35S]GTPγS, [35S]guanosine-5′-O-(3-thio)triphosphate; (1DMe)Y8Fa, DYL(NMe)FQPQRF-NH2; rNPSF, rat neuropeptide SF; r, rat; b, bovine; h, human; HEK, human embryonic kidney cell; FMRFamide, phenylalanyl-methionyl-arginyl-phenylalaninamide; 125I-Y8Fa, 125I-YLFQPQRFamide; 125I-EYF, 125I-EYWSLAAPQRF-NH2; RT, room temperature; BSA, bovine serum albumin; TB, total binding; NSB, nonspecific binding; SB, specific binding; PTX, pertussis toxin; VIP, vasoactive intestinal polypeptide.

    • Received November 25, 2002.
    • Accepted February 14, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 305 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 305, Issue 3
1 Jun 2003
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Research ArticleNEUROPHARMACOLOGY

Prolactin Releasing Peptide Has High Affinity and Efficacy at Neuropeptide FF2 Receptors

Mia Engström, Annika Brandt, Siegfried Wurster, Juha-Matti Savola and Pertti Panula
Journal of Pharmacology and Experimental Therapeutics June 1, 2003, 305 (3) 825-832; DOI: https://doi.org/10.1124/jpet.102.047118

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Research ArticleNEUROPHARMACOLOGY

Prolactin Releasing Peptide Has High Affinity and Efficacy at Neuropeptide FF2 Receptors

Mia Engström, Annika Brandt, Siegfried Wurster, Juha-Matti Savola and Pertti Panula
Journal of Pharmacology and Experimental Therapeutics June 1, 2003, 305 (3) 825-832; DOI: https://doi.org/10.1124/jpet.102.047118
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