Journal of Molecular Medicine

, Volume 77, Issue 6, pp 495–504 | Cite as

The quest for novel bioactive peptides utilizing orphan seven-transmembrane-domain receptors

  • Shuji Hinuma
  • Haruo Onda
  • Masahiko Fujino
REVIEW

Abstract

Various sorts of bioactive molecules including hormones, neurotransmitters, and chemokines transmit signals into cells by binding to so-called seven-transmembrane-domain receptors (7TMRs). The recent progress in cDNA and genome DNA analyses has brought the discovery of numerous genes encoding ligand-unknown "orphan" 7TMRs. We have developed a strategy to identify the ligands of orphan 7TMRs by monitoring specific signal transductions induced in cells expressing orphan 7TMRs. Employing this method, we succeeded in identifying the natural ligands of the orphan 7TMRs, hGR3, and APJ. The ligand peptide identified for hGR3 was found to show a specific prolactin release promoting activity in rat anterior pituitary cells in in vitro culture and was therefore named "prolactin-releasing peptide." We named another novel bioactive peptide "apelin," for "APJ endogenous ligand." Although the biological functions of apelin are still under investigation, APJ reportedly acts as a coreceptor in the process of human immunodeficiency virus infection. We believe that the identification of orphan 7TMR ligands will provide clues to reveal the unknown regulatory mechanisms of various physiological phenomena and opportunities for novel drug discovery in the future.

Key words Orphan seven-transmembrane-domain receptor Ligand Peptide Prolactin-releasing peptide Apelin 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Shuji Hinuma
    • 1
  • Haruo Onda
    • 1
  • Masahiko Fujino
    • 1
  1. 1.Discovery Research Laboratories 1, Discovery Research Division, Takeda Chemical Industries Ltd., Wadai 10, Tsukuba, Ibaraki 300-4293, Japan, e-mail: Hinuma_Shuji@takeda.co.jp, Tel.: +81-298-645035, Fax: +81-298-645000JP

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