Growth hormone secretagogue receptor family members and ligands.
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, GPR38, 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.
Smith
R G
RG
Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030-3498, USA. rsmith@bcm.tmc.edu
Leonard
R
R
Bailey
A R
AR
Palyha
O
O
Feighner
S
S
Tan
C
C
Mckee
K K
KK
Pong
S S
SS
Griffin
P
P
Howard
A
A
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects; D015698:Genomic Library; D054439:Ghrelin; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D009037:Motilin / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D036361:Peptide Hormones; D010455:Peptides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D017386:Sequence Homology, Amino Acid; D013141:Spiro Compounds / Q000378:metabolism / Q000494:pharmacology; D013777:Tetrazoles / Q000378:metabolism; D014020:Tissue Extracts / Q000494:pharmacology
D001552:Benzazepines; D054439:Ghrelin; D007211:Indoles; D009842:Oligopeptides; D036361:Peptide Hormones; D010455:Peptides; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013141:Spiro Compounds; D013777:Tetrazoles; D014020:Tissue Extracts; C081455:L 692429; C041048:growth hormone releasing hexapeptide; D009037:Motilin; D013007:Growth Hormone-Releasing Hormone; D000241:Adenosine; C094817:ibutamoren mesylate