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New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals

Abstract

Only a few RFamide peptides have been identified in mammals, although they have been abundantly found in invertebrates. Here we report the identification of a human gene that encodes at least three RFamide-related peptides, hRFRP-1–3. Cells transfected with a seven-transmembrane-domain receptor, OT7T022, specifically respond to synthetic hRFRP-1 and hRFRP-3 but not to hRFRP-2. RFRP and OT7T022 mRNAs are expressed in particular regions of the rat hypothalamus, and intracerebroventricular administration of hRFRP-1 increases prolactin secretion in rats. Our results indicate that a variety of RFamide-related peptides may exist and function in mammals.

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Figure 1: Amino-acid sequences of human, bovine, rat and mouse RFRP preproproteins.
Figure 2: Comparison of amino-acid sequences of known RFamide peptides and RFRPs.
Figure 3: Amino-acid sequences of rat and human OT7T022.
Figure 4: Analyses for interaction between RFRPs and OT7T022.
Figure 5: Tissue distributions of RFRP and OT7T022 mRNAs in rats.
Figure 6: Localizations of RFRP and OT7T022 mRNAs in rat brain.
Figure 7: Effects of RFRP on plasma PRL levels in rats.

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Acknowledgements

We thank Y. Sumino for discussions, M. Mori for CHO cells expressing rat OT7T022, and K. Yamamoto for collaboration in the database search.

Correspondence and requests for materials should be addressed to S.H. The nucleotide sequences encoding the human, bovine, rat and mouse RFRP preproproteins and human and rat OT7T022 have been deposited at GenBank under accession nos AB040290, AB040291, AB040288, AB040289, AB040104, and AB040103, respectively.

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Correspondence to Shuji Hinuma.

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Correspondence and requests for materials should be addressed to S H. The nucleotide sequences encoding the human, bovine, rat and mouse RFRP preproproteins and human and rat OT7T022 have been deposited at GenBank under accession nos AB040290, AB040291, AB040288, AB040289, AB040104 and AB040103, respectively.

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Hinuma, S., Shintani, Y., Fukusumi, S. et al. New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals. Nat Cell Biol 2, 703–708 (2000). https://doi.org/10.1038/35036326

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