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

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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

J Mol Med. 1999 Jun;77(6):495-504. Unique Identifier : AIDSLINE MED/99402049
Hinuma S; Onda H; Fujino M; Discovery Research Division, Takeda Chemical Industries, Ltd.,; Tsukuba, Ibaraki, Japan. Hinuma_Shuji@takeda.co.jp

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.

Keywords: JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL Animal Carrier Proteins/*ISOLATION & PURIF/METABOLISM Human Hypothalamic Hormones/*ISOLATION & PURIF/METABOLISM Ligands Molecular Sequence Data Neuropeptides/*ISOLATION & PURIF/METABOLISM Receptors, Cell Surface/*AGONISTS/GENETICS/*ISOLATION & PURIF Sequence Alignment
991230
A99C1019

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1999. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1999. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .