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Growth hormone secretagogue receptor family members and ligands

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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.

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Author information

Authors and Affiliations

  1. Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, M320, One Baylor Plaza, 77030-3498, Houston, TX

    Roy G. Smith & Alex R. T. Bailey

  2. Merck Research Laboratories, Rahway, NJ

    Roy G. Smith, Reid Leonard, Oksana Palyha, Scott Feighner, Carina Tan, Karen Kulju McKee, Sheng-Shung Pong, Pat Griffin & Andrew Howard

Authors
  1. Roy G. Smith

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  2. Reid Leonard

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  3. Alex R. T. Bailey

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  4. Oksana Palyha

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  5. Scott Feighner

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  6. Carina Tan

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  7. Karen Kulju McKee

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  8. Sheng-Shung Pong

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  9. Pat Griffin

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  10. Andrew Howard

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Corresponding author

Correspondence to Roy G. Smith.

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