Endocrine

, Volume 14, Issue 1, pp 9–14

Growth hormone secretagogue receptor family members and ligands

  • Roy G. Smith
  • Reid Leonard
  • Alex R. T. Bailey
  • Oksana Palyha
  • Scott Feighner
  • Carina Tan
  • Karen Kulju McKee
  • Sheng-Shung Pong
  • Pat Griffin
  • Andrew Howard
Article

Abstract

We have previously reported the cloning and characterization of a new orphan G-protein-coupled receptor (GPC-R), the growth hormone secretagogue receptor (GHS-R), and shown that this receptor mediates the activity of the growth hormone-releasing peptides (GHRPs) and nonpeptide ligands such as L-692,429 and MK-0677. Because the GHS-R obviously does not belong to any of the known GPC-R subfamilies, we searched for GHS-R family members by screening a human genomic library using low-stringency hybridization and screening a Pufferfish genomic library. The Pufferfish was selected because of its compact genome. From the human genomic library, a homolog, GPR 38, with 52% identity to the GHS-R was isolated. From the Pufferfish library, three family members were isolated. The Pufferfish gene having 58% identity to the GHS-R, on expression in HEK293 cells, was activated with GHRP-6 and MK-0677. These results indicate that the GHS-R has been conserved for at least 400 million years and that the Pufferfish genome is appropriate for isolation of GHS-R family members. In our search for endogenous ligands for the orphan receptors GHS-R and GPR38, we showed that adenosine is a partial agonist of the GHS-R and that motilin is the endogenous ligand for GPR38. We also confirmed that the endogenous ligand ghrelin is a full agonist of the GHS-R.

Key Words

Growth hormone secretagogue receptor motilin adenosine 

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Copyright information

© Humana Press Inc. 2001

Authors and Affiliations

  • Roy G. Smith
    • 1
    • 2
  • Reid Leonard
    • 2
  • Alex R. T. Bailey
    • 1
  • Oksana Palyha
    • 2
  • Scott Feighner
    • 2
  • Carina Tan
    • 2
  • Karen Kulju McKee
    • 2
  • Sheng-Shung Pong
    • 2
  • Pat Griffin
    • 2
  • Andrew Howard
    • 2
  1. 1.Huffington Center on Aging and Department of Molecular and Cellular BiologyBaylor College of MedicineHouston
  2. 2.Merck Research LaboratoriesRahway

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