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.
Similar content being viewed by others
References
Howard, A. D., Feighner, S. D., Cully, D. F., et al. (1996). Science 273, 974–977.
McKee, K. K., Tan, C. P., Palyha, O. C., Liu, J., Feighner, S. D., Hreniuk, D. L., Smith, R. G., Howard, A. D., and Van der Ploeg, L. H. T. (1997). Genomics 46, 426–434.
Tan, C. P., McKee, K. K., Liu, Q., Palyha, O. C., Feighner, S. D., Hreniuk, D. L., Smith, R. G., and Howard, A. D. (1998). Genomics 52, 223–229.
Brenner, S., Elgar, G., Sandford, R., Macrae, A., Venkatesh, B., and Aparicio, S. (1993). Nature 366, 265–268.
Baxendale, S., Abdulla, S., Elgar, G., Buck, D., Berks, M., Micklem, G., Durbin, R., Bates, G., Brenner, S., and Beck, S. (1995). Nat. Genet. 10(1), 67–76.
Elgar, G., Rattray, F., Greystrong J., and Brenner, S. (1995). Genomics 27(3), 442–446.
Mason, P. J., Stevens, D. J., Luzzatto, L., Brenner, S., and Aparicio, S. (1995). Genomics 26(3), 587–591.
Macrae, A. D. and Brenner, S. (1995). Genomics 25(2), 436–446.
Macrae, A. D. and Brenner, S. (1994). Genomics 24(1), 176–178.
Palyha, O. C., Feighner, S. D., Tan, C. P., McKee, K. K., Hreniuk, D. L., Gao, Y.-D., Schleim, K. D., Yang, L., Morriello, G. J., Nargund, R., Patchett, A. A., Howard, A. D., and Smith, R. G. (2000). Mol. Endocrinol. 14(1), 160–169.
Feighner, S. D., Howard, A. D., Prendergast, K., et al. (1998). Mol. Endocrinol. 12, 137–145.
Cheng, K., Wei, L., Chaung, L., Chan, W. W.-S., Butler, B., and Smith, R. G. (1997). J. Endocrinol. 152, 155–158.
Feighner, S. D., Tan, C. P., McKee, K. K., et al. (1999). Science 284, 2184–2188.
Daikh, D. I., Douglass, J. O., and Adelman, J. P. (1989). DNA 8(8), 615–621.
Yano, H., Seino, Y., Fujita, J., Yamada, Y., Inagaki, N., Takeda, J., Bell, G. I., Eddy, R. L., Fan, Y. S., Byers M. G., Shows, T. B., and Imura, H. (1989). FEBS Lett. 249, 248–252.
Sakai, T., Satoh, M., Sonobe, K., Nakajima, M., Shiba, Y., and Itoh, Z. (1994). Regul. Pept. 53(3), 249–257.
Depoortere, I., Van Assche, G., and Peeters, T. L. (1997). Brain Res. 777(1–2), 103–109.
Poitras, P., Miller, P., Dickner, M., Mao, Y. K., Daniel, E. E., St-Pierre, S., and Trudel, L. (1996). Peptides 17(4), 701–707.
Peeters, T. L., Bormans, V., and Vantrappen, G. (1988). Regul. Pept. 23(2), 171–182.
Depoortere, I., Peeters, T. L., and Vantrappen, G. (1991). Peptides 12(1), 89–94.
Depoortere, I., Peeters, T. L,, and Vantrappen, G. (1993). Peptides 14(6), 1153–1157.
Depoortere, I. and Peeters, T. L. (1997). Am. J. Physiol. 272(5 Pt1), G994-G999.
Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., and Kangawa, K. (1999). Nature 402(6762), 656–660.
Murphy, D., Si-Hoe, S.-L., Brenner, S., and Venkatesh, B. (1998). BioEssays 20, 741–749.
Guan, X.-M., Yu, H., Palyha, O. C., McKee, K. K., Feighner, S. D., Sirinathsinghji, D. J. S., Smith, R. G., Van der Ploeg, L. H. T., and Howard, A. D. (1997). Mol. Brain Res. 48, 23–29.
DeGennaro Colonna, V., Rossoni, G., Beruareggi, M., Muller, E. E., and Berti, F. (1997). Cardiologia, 42(11), 1165–1172.
Rossoni, G., De Gennaro Colonna, V., Bernareggi, M., Polvani, G. L., Muller, E. E., and Berti, F. (1998). J. Cardiovasc. Pharmacol. 32(2), 260–265.
Rossoni, G., Locatelli, V., De Gennaro Colonna, V., Torsello, A., Schweiger, F., Boghen, M., Nilsson, M., Bernareggi, M., Muller, E. E., and Berti, F. (1999). J. Cardiovasc. Pharmacol. 34(3), 454–460.
Bisi, G., Podio, V., Valetto, M. R., Broglio, F., Bertuccio, G., Aimaretti, G., Pelosi, E., Del Rio, G., Muccioli, G., Ong, H., Boghen, M. F., Deghenghi, R., and Ghigo E. (1999). Eur. J. Pharmacol. 381(1), 31–38.
Locatelli, V., Rossoni, G., Schweiger, F., Torsello, A., de Gennaro Colonna, V., Bernareggi, M., Deghenghi, R., Muller, E. E., and Berti, F. (1999). Endocrinology 140, 4024–4031.
Tivesten, A., Bollano, E., Caidahl, K., Kujacic, V., Sun, X. Y., Hedner, T., Hjalmarson, A., Bengtsson, B. A., and Isgaard, J. (2000). Endocrinology 141(1), 60–66.
Premont, J., Perez, M., and Bockaert, J. (1977). Mol. Pharmacol. 13, 662–670.
Ferre, S., Fredholm, B. B., Morelli, M., Popoli, P., and Fuxe, K. (1997). TINS 20(10), 482–487.
Ongini, E. and Fredholm, B. B. (1996). Trends Pharmacol. Sci. 17, 364–372.
Porter, J. C., Kedzierski, W., Aguila-Mansilla, N., and Jorquera, B. A. (1990). Endocrinology 126, 2474–2481.
Porter, J. C., Aguila-Mansilla, N., Ramin, S. M., Kozlowski, G. P., and Kedzierski, W. (1991). Endocrinology 129, 2477–2485.
Porter, J. C., Ijames, C. F., Wang, T.-C L., and Markey, S. P. (1995). Proc. Natl. Acad. Sci. USA 92, 5351–5355.
Smith R. G., Feighner, S., Prendergast, K., Guan, X., and Howard, A. (1999). Trends Endocrinol. Metab. 10(4), 128–135.
Smith, R. G., Griffin, P. R., Xu, Y., et al. (2000). Adenosine: a partial agonist of the growth hormone secretagogue receptor. Biochem. Biophys. Res. Commun. 276(3), 1306–1313.
Tullin, S., Hansen, B. S., Ankersen, M., Moller, J., Von Cappelen, K. A. and Thim, L. (2000) Adenosine is an agonist of the growth hormone secretagogue receptor. Endocrinology 141(9), 3397–3402.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Smith, R.G., Leonard, R., Bailey, A.R.T. et al. Growth hormone secretagogue receptor family members and ligands. Endocr 14, 9–14 (2001). https://doi.org/10.1385/ENDO:14:1:009
Issue Date:
DOI: https://doi.org/10.1385/ENDO:14:1:009