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Gene Review

Crhr2  -  corticotropin releasing hormone receptor 2

Rattus norvegicus

Synonyms: CRF-R-2, CRF-R2, CRFR-2, CRH-R-2, CRH-R2, ...
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Disease relevance of Crhr2

  • The present study demonstrates using in situ autoradiography that CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2) mRNA in the rat anterior pituitary is changed by intermittent hypoxia, cold, restraint, alone and in combination [1].
  • Thus, alterations of CRHR-2 mRNA are dependent on the strain or experimental condition rather than as a consequence of hypertension [2].

Psychiatry related information on Crhr2


High impact information on Crhr2


Chemical compound and disease context of Crhr2

  • Since alterations in heart CRHR-2 mRNA, as seen in SHR and DOCA, were bi-directional, the role of heart CRHR-2 in the regulation of hypertension remains to be elucidated [2].

Biological context of Crhr2

  • In contrast, a CRF2 receptor antagonist (Astressin2-B) blocked the effects of CRF-like peptides on the antral muscle contractions [6].
  • On the other hand, CRF2 alpha and CRF2 beta receptor mRNAs were undetectable both in control and stressed animals throughout the estrous cycle [7].
  • Furthermore, the fact that CRF-R2 is membrane bound at synapses, while CRF-R1 is not, suggests that ligands couple to CRF-R2 via synaptic transmission and to CRF-R1 via volume transmission [8].
  • The previous finding that type-1 CRHR mRNA is not detected in heart leads us to speculate that systemic administration of CRH induces hypotensive effects through CRHR-2, and that alterations in CRHR-2 in the heart may be implicated in blood pressure regulation [2].
  • These results are consistent with a role for CRF2 activation in mediating some of the complex interactions of CRF (or urocortin) with regulation of food intake in the developing rat [3].

Anatomical context of Crhr2


Associations of Crhr2 with chemical compounds

  • After acute withdrawal from a chronic cocaine administration regimen, CRF1 activation remained facilitatory, but CRF2 activation facilitated rather than depressed LSMLN EPSCs [10].
  • LPS administration still caused a significant suppression of CRF R2 mRNA levels in the anterior pituitary of adrenalectomized rats [11].
  • Subcutaneous corticosterone injections also resulted in significant suppression of CRF R2 mRNA levels in the pituitary, suggesting that glucocorticoids are involved in modulating CRF R2 mRNA levels in the pituitary under stress [11].
  • Incubation with CRF R2 ligands or dexamethasone reduced CRF R2beta mRNA levels [12].
  • These data suggest that CRF1 and CRF2 activation within the DRN affect 5-HT neurons in opponent fashion [13].

Physical interactions of Crhr2

  • The mature peptide is rapidly released, and exerts autocrine/paracrine protective effects through the cardiac CRH-R2 receptor which preferentially binds urocortin [14].
  • Urocortin (UCN), is a peptide related to hypothalamic corticotrophin releasing hormone (CRF) and binds with high affinity to the CRF-R2 beta receptor which is expressed in the heart [15].

Regulatory relationships of Crhr2


Other interactions of Crhr2

  • Taken together, these findings suggest that in inflammatory pain CRH-induced peripheral antinociception is mediated via both CRH R1 and CRH R2 located on END containing immune cells within inflamed sites [9].
  • Repeated immobiliza tion also lowered plasma insulin and leptin concentrations and VMH CRHR-2 mRNA levels [17].
  • These results suggest that the CRF2 receptor is involved in motor suppressive effects as well as anxiolytic and anorectic effects of Ucn 2 and Ucn 3 [18].
  • The effects of Ucn II were attenuated by astressin2-B, a specific antagonist of CRH-R2, and/or H89, an inhibitor of protein kinase A (PKA) [19].

Analytical, diagnostic and therapeutic context of Crhr2

  • Frozen ovaries were mounted on a microtome, cut into 30-microns slices, and then processed for the detection of mRNAs encoding CRF1, CRF2 alpha, or CRF2 beta receptors by in situ hybridization histochemistry using 35S-labeled riboprobes [7].
  • CRF1 but not CRF2, know down produced a significant anxiolytic-like effect in the Defensive Withdrawal relative to vehicle-treated and two missense oligonucleotide negative control groups [20].
  • The present studies examined the potential functional significance of the CRF2 receptor in relation to the CRF1 receptor using two animal models of anxiety and endocrine reactivity to a stressor [20].
  • Therefore, we examined the effect of glucocorticoid treatment, adrenalectomy, and systemic administration of urocortin, a possible endogenous ligand for CRHR-2, on heart CRHR-2 mRNA levels in male Wistar rats, using in situ hybridization histochemistry [21].
  • We examined the effects of various pretreatments with K41498, a selective CRF2 receptor antagonist, atropine, 6-hydroxydopamine, hepatic plexus denervation, or hepatic branch vagotomy, respectively [22].


  1. Corticotropin-releasing factor receptor type 1 and 2 mRNA expression in the rat anterior pituitary is modulated by intermittent hypoxia, cold and restraint. Wang, T.Y., Chen, X.Q., Du, J.Z., Xu, N.Y., Wei, C.B., Vale, W.W. Neuroscience (2004) [Pubmed]
  2. Type 2 corticotropin-releasing hormone receptor mRNA expression in the heart in hypertensive rats. Makino, S., Asaba, K., Takao, T., Hashimoto, K. Life Sci. (1998) [Pubmed]
  3. Corticotropin releasing factor receptor type II (CRF2) messenger ribonucleic acid levels in the hypothalamic ventromedial nucleus of the infant rat are reduced by maternal deprivation. Eghbal-Ahmadi, M., Hatalski, C.G., Avishai-Eliner, S., Baram, T.Z. Endocrinology (1997) [Pubmed]
  4. Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Chen, C.Y., Inui, A., Asakawa, A., Fujino, K., Kato, I., Chen, C.C., Ueno, N., Fujimiya, M. Gastroenterology (2005) [Pubmed]
  5. Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression. Chalmers, D.T., Lovenberg, T.W., De Souza, E.B. J. Neurosci. (1995) [Pubmed]
  6. Endogenous expression and in vitro study of CRF-related peptides and CRF receptors in the rat gastric antrum. Porcher, C., Peinnequin, A., Pellissier, S., Meregnani, J., Sinniger, V., Canini, F., Bonaz, B. Peptides (2006) [Pubmed]
  7. Stress-induced genetic expression of a selective corticotropin-releasing factor-receptor subtype within the rat ovaries: an effect dependent on the ovulatory cycle. Nappi, R.E., Rivest, S. Biol. Reprod. (1995) [Pubmed]
  8. Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum. Swinny, J.D., Kalicharan, D., Blaauw, E.H., Ijkema-Paassen, J., Shi, F., Gramsbergen, A., van der Want, J.J. Eur. J. Neurosci. (2003) [Pubmed]
  9. Involvement of corticotropin-releasing hormone receptor subtypes 1 and 2 in peripheral opioid-mediated inhibition of inflammatory pain. Mousa, S.A., Bopaiah, C.P., Stein, C., Schäfer, M. Pain (2003) [Pubmed]
  10. Chronic cocaine administration switches corticotropin-releasing factor2 receptor-mediated depression to facilitation of glutamatergic transmission in the lateral septum. Liu, J., Yu, B., Orozco-Cabal, L., Grigoriadis, D.E., Rivier, J., Vale, W.W., Shinnick-Gallagher, P., Gallagher, J.P. J. Neurosci. (2005) [Pubmed]
  11. Corticotropin-releasing factor receptor type 2 messenger ribonucleic acid in rat pituitary: localization and regulation by immune challenge, restraint stress, and glucocorticoids. Kageyama, K., Li, C., Vale, W.W. Endocrinology (2003) [Pubmed]
  12. Regulation of corticotropin-releasing factor receptor type 2 beta messenger ribonucleic acid in the rat cardiovascular system by urocortin, glucocorticoids, and cytokines. Kageyama, K., Gaudriault, G.E., Bradbury, M.J., Vale, W.W. Endocrinology (2000) [Pubmed]
  13. Microinjection of urocortin 2 into the dorsal raphe nucleus activates serotonergic neurons and increases extracellular serotonin in the basolateral amygdala. Amat, J., Tamblyn, J.P., Paul, E.D., Bland, S.T., Amat, P., Foster, A.C., Watkins, L.R., Maier, S.F. Neuroscience (2004) [Pubmed]
  14. CRH-like peptides protect cardiac myocytes from lethal ischaemic injury. Brar, B.K., Stephanou, A., Okosi, A., Lawrence, K.M., Knight, R.A., Marber, M.S., Latchman, D.S. Mol. Cell. Endocrinol. (1999) [Pubmed]
  15. Urocortin protects against ischemic injury via a MAPK-dependent pathway. Latchman, D.S. Trends Cardiovasc. Med. (2001) [Pubmed]
  16. Characterization of the relaxant action of urocortin, a new peptide related to corticotropin-releasing factor in the rat isolated basilar artery. Schilling, L., Kanzler, C., Schmiedek, P., Ehrenreich, H. Br. J. Pharmacol. (1998) [Pubmed]
  17. Decreased type 2 corticotropin-releasing hormone receptor mRNA expression in the ventromedial hypothalamus during repeated immobilization stress. Makino, S., Asaba, K., Nishiyama, M., Hashimoto, K. Neuroendocrinology (1999) [Pubmed]
  18. Effects of urocortin 2 and 3 on motor activity and food intake in rats. Ohata, H., Shibasaki, T. Peptides (2004) [Pubmed]
  19. Effects of urocortin II on neonatal rat cardiac myocytes and non-myocytes. Ikeda, K., Tojo, K., Otsubo, C., Udagawa, T., Hosoya, T., Tajima, N., Nakao, K., Kawamura, M. Peptides (2005) [Pubmed]
  20. Corticotropin-releasing factor CRF1, but not CRF2, receptors mediate anxiogenic-like behavior. Heinrichs, S.C., Lapsansky, J., Lovenberg, T.W., De Souza, E.B., Chalmers, D.T. Regul. Pept. (1997) [Pubmed]
  21. Regulation of type-2 corticotropin-releasing hormone receptor mRNA in rat heart by glucocorticoids and urocortin. Asaba, K., Makino, S., Nishiyama, M., Hashimoto, K. J. Cardiovasc. Pharmacol. (2000) [Pubmed]
  22. Effect of central corticotropin releasing factor on hepatic circulation in rats: the role of the CRF2 receptor in the brain. Yoneda, M., Nakamura, K., Nakade, Y., Tamano, M., Kono, T., Watanobe, H., Shimada, T., Hiraishi, H., Terano, A. Gut (2005) [Pubmed]
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