Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Mar 28;92(7):2969–2973. doi: 10.1073/pnas.92.7.2969

Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart.

M Perrin 1, C Donaldson 1, R Chen 1, A Blount 1, T Berggren 1, L Bilezikjian 1, P Sawchenko 1, W Vale 1
PMCID: PMC42340  PMID: 7708757

Abstract

Corticotropin-releasing factor (CRF; corticoliberin) regulates the secretion of corticotropin (ACTH) and beta-endorphin and has a broad range of effects on the nervous, endocrine, reproductive, cardiovascular, gastrointestinal, and immune systems. Recently, human, rat, and mouse CRF receptors (CRF-R) have been cloned and functionally and anatomically characterized. We report here the cloning of a second CRF-R cDNA (CRF-RB), which encodes a protein of 431 amino acids, which is 16 amino acids longer and 68% similar to the previously cloned CRF-R, CRF-RA. When transiently expressed in COS-M6 cells, CRF-RB binds CRF with high affinity [Kd = 1.2 (0.57-2.5)nM] and transduces the CRF-stimulated signal of the accumulation of intracellular cAMP, which is inhibited by a CRF antagonist. Comparison of the amino acid sequences of CRF-RB and the previously cloned receptor reveals major differences in the N-terminal domain and in the extracellular loops, whereas the sequences of the intracellular loops are nearly identical. CRF-RB and related transcripts are expressed in the heart, as well as in other tissues, including the gastrointestinal tract, epididymis, and brain.

Full text

PDF
2969

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chang C. P., Pearse R. V., 2nd, O'Connell S., Rosenfeld M. G. Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain. Neuron. 1993 Dec;11(6):1187–1195. doi: 10.1016/0896-6273(93)90230-o. [DOI] [PubMed] [Google Scholar]
  2. Chen R., Lewis K. A., Perrin M. H., Vale W. W. Expression cloning of a human corticotropin-releasing-factor receptor. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8967–8971. doi: 10.1073/pnas.90.19.8967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. De Souza E. B., Perrin M. H., Insel T. R., Rivier J., Vale W. W., Kuhar M. J. Corticotropin-releasing factor receptors in rat forebrain: autoradiographic identification. Science. 1984 Jun 29;224(4656):1449–1451. doi: 10.1126/science.6328656. [DOI] [PubMed] [Google Scholar]
  4. De Souza E. B., Whitehouse P. J., Kuhar M. J., Price D. L., Vale W. W. Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease. Nature. 1986 Feb 13;319(6054):593–595. doi: 10.1038/319593a0. [DOI] [PubMed] [Google Scholar]
  5. Dohlman H. G., Thorner J., Caron M. G., Lefkowitz R. J. Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem. 1991;60:653–688. doi: 10.1146/annurev.bi.60.070191.003253. [DOI] [PubMed] [Google Scholar]
  6. Grunt M., Haug C., Duntas L., Pauschinger P., Maier V., Pfeiffer E. F. Dilatory and inotropic effects of corticotropin-releasing factor (CRF) on the isolated heart. Effects on atrial natriuretic peptide (ANP) release. Horm Metab Res. 1992 Feb;24(2):56–59. doi: 10.1055/s-2007-1003255. [DOI] [PubMed] [Google Scholar]
  7. Hanani M., Wood J. D. Corticotropin-releasing hormone excites myenteric neurons in the guinea-pig small intestine. Eur J Pharmacol. 1992 Jan 28;211(1):23–27. doi: 10.1016/0014-2999(92)90256-4. [DOI] [PubMed] [Google Scholar]
  8. Jüppner H., Schipani E., Bringhurst F. R., McClure I., Keutmann H. T., Potts J. T., Jr, Kronenberg H. M., Abou-Samra A. B., Segre G. V., Gardella T. J. The extracellular amino-terminal region of the parathyroid hormone (PTH)/PTH-related peptide receptor determines the binding affinity for carboxyl-terminal fragments of PTH-(1-34). Endocrinology. 1994 Feb;134(2):879–884. doi: 10.1210/endo.134.2.8299582. [DOI] [PubMed] [Google Scholar]
  9. Kawahito Y., Sano H., Kawata M., Yuri K., Mukai S., Yamamura Y., Kato H., Chrousos G. P., Wilder R. L., Kondo M. Local secretion of corticotropin-releasing hormone by enterochromaffin cells in human colon. Gastroenterology. 1994 Apr;106(4):859–865. doi: 10.1016/0016-5085(94)90743-9. [DOI] [PubMed] [Google Scholar]
  10. Kosugi S., Kohn L. D., Akamizu T., Mori T. The middle portion in the second cytoplasmic loop of the thyrotropin receptor plays a crucial role in adenylate cyclase activation. Mol Endocrinol. 1994 Apr;8(4):498–509. doi: 10.1210/mend.8.4.7914349. [DOI] [PubMed] [Google Scholar]
  11. Lenz H. J. Extrapituitary effects of corticotropin-releasing factor. Horm Metab Res Suppl. 1987;16:17–23. [PubMed] [Google Scholar]
  12. Lovenberg T. W., Liaw C. W., Grigoriadis D. E., Clevenger W., Chalmers D. T., De Souza E. B., Oltersdorf T. Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):836–840. doi: 10.1073/pnas.92.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Millan M. A., Samra A. B., Wynn P. C., Catt K. J., Aguilera G. Receptors and actions of corticotropin-releasing hormone in the primate pituitary gland. J Clin Endocrinol Metab. 1987 May;64(5):1036–1041. doi: 10.1210/jcem-64-5-1036. [DOI] [PubMed] [Google Scholar]
  14. Muglia L. J., Jenkins N. A., Gilbert D. J., Copeland N. G., Majzoub J. A. Expression of the mouse corticotropin-releasing hormone gene in vivo and targeted inactivation in embryonic stem cells. J Clin Invest. 1994 May;93(5):2066–2072. doi: 10.1172/JCI117201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  16. Nieuwenhuijzen Kruseman A. C., Linton E. A., Lowry P. J., Rees L. H., Besser G. M. Corticotropin-releasing factor immunoreactivity in human gastrointestinal tract. Lancet. 1982 Dec 4;2(8310):1245–1246. doi: 10.1016/s0140-6736(82)90105-2. [DOI] [PubMed] [Google Scholar]
  17. O'Dowd B. F., Hnatowich M., Regan J. W., Leader W. M., Caron M. G., Lefkowitz R. J. Site-directed mutagenesis of the cytoplasmic domains of the human beta 2-adrenergic receptor. Localization of regions involved in G protein-receptor coupling. J Biol Chem. 1988 Nov 5;263(31):15985–15992. [PubMed] [Google Scholar]
  18. Okamoto T., Murayama Y., Hayashi Y., Inagaki M., Ogata E., Nishimoto I. Identification of a Gs activator region of the beta 2-adrenergic receptor that is autoregulated via protein kinase A-dependent phosphorylation. Cell. 1991 Nov 15;67(4):723–730. doi: 10.1016/0092-8674(91)90067-9. [DOI] [PubMed] [Google Scholar]
  19. Orth D. N. Corticotropin-releasing hormone in humans. Endocr Rev. 1992 May;13(2):164–191. doi: 10.1210/edrv-13-2-164. [DOI] [PubMed] [Google Scholar]
  20. Perrin M. H., Donaldson C. J., Chen R., Lewis K. A., Vale W. W. Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor. Endocrinology. 1993 Dec;133(6):3058–3061. doi: 10.1210/endo.133.6.8243338. [DOI] [PubMed] [Google Scholar]
  21. Perrin M. H., Haas Y., Rivier J. E., Vale W. W. Corticotropin-releasing factor binding to the anterior pituitary receptor is modulated by divalent cations and guanyl nucleotides. Endocrinology. 1986 Mar;118(3):1171–1179. doi: 10.1210/endo-118-3-1171. [DOI] [PubMed] [Google Scholar]
  22. Petrusz P., Merchenthaler I., Maderdrut J. L., Heitz P. U. Central and peripheral distribution of corticotropin-releasing factor. Fed Proc. 1985 Jan;44(1 Pt 2):229–235. [PubMed] [Google Scholar]
  23. Potter E., Sutton S., Donaldson C., Chen R., Perrin M., Lewis K., Sawchenko P. E., Vale W. Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8777–8781. doi: 10.1073/pnas.91.19.8777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rivier J. E., Porter J., Rivier C. L., Perrin M., Corrigan A., Hook W. A., Siraganian R. P., Vale W. W. New effective gonadotropin releasing hormone antagonists with minimal potency for histamine release in vitro. J Med Chem. 1986 Oct;29(10):1846–1851. doi: 10.1021/jm00160a008. [DOI] [PubMed] [Google Scholar]
  25. Saitoh M., Hasegawa J., Mashiba H. Effect of corticotropin-releasing factor on the electrical and mechanical activities of the guinea-pig ventricular myocardium. Gen Pharmacol. 1990;21(3):337–342. doi: 10.1016/0306-3623(90)90834-9. [DOI] [PubMed] [Google Scholar]
  26. Sheldon R. J., Qi J. A., Porreca F., Fisher L. A. Gastrointestinal motor effects of corticotropin-releasing factor in mice. Regul Pept. 1990 Apr 24;28(2):137–151. doi: 10.1016/0167-0115(90)90013-m. [DOI] [PubMed] [Google Scholar]
  27. Udelsman R., Harwood J. P., Millan M. A., Chrousos G. P., Goldstein D. S., Zimlichman R., Catt K. J., Aguilera G. Functional corticotropin releasing factor receptors in the primate peripheral sympathetic nervous system. Nature. 1986 Jan 9;319(6049):147–150. doi: 10.1038/319147a0. [DOI] [PubMed] [Google Scholar]
  28. Vale W., Spiess J., Rivier C., Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science. 1981 Sep 18;213(4514):1394–1397. doi: 10.1126/science.6267699. [DOI] [PubMed] [Google Scholar]
  29. Vita N., Laurent P., Lefort S., Chalon P., Lelias J. M., Kaghad M., Le Fur G., Caput D., Ferrara P. Primary structure and functional expression of mouse pituitary and human brain corticotrophin releasing factor receptors. FEBS Lett. 1993 Nov 29;335(1):1–5. doi: 10.1016/0014-5793(93)80427-v. [DOI] [PubMed] [Google Scholar]
  30. Webster E. L., De Souza E. B. Corticotropin-releasing factor receptors in mouse spleen: identification, autoradiographic localization, and regulation by divalent cations and guanine nucleotides. Endocrinology. 1988 Feb;122(2):609–617. doi: 10.1210/endo-122-2-609. [DOI] [PubMed] [Google Scholar]
  31. Williams C. L., Peterson J. M., Villar R. G., Burks T. F. Corticotropin-releasing factor directly mediates colonic responses to stress. Am J Physiol. 1987 Oct;253(4 Pt 1):G582–G586. doi: 10.1152/ajpgi.1987.253.4.G582. [DOI] [PubMed] [Google Scholar]
  32. Yoon D. J., Sklar C., David R. Presence of immunoreactive corticotropin-releasing factor in rat testis. Endocrinology. 1988 Feb;122(2):759–761. doi: 10.1210/endo-122-2-759. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES