- corticotropin releasing hormone receptor 1
- Available assay modes
- Agonist, Inverse agonist, Antagonist, PAM, NAM
- à la carte, Oncology, Psychiatry, Neurology, Dermatology, Musculoskeletal, Human non-orphan GPCRs
Corticotropin-releasing factor receptorsCorticotropin-releasing factor (CRF) receptors are activated by the endogenous peptides corticotrophin-releasing hormone, a 41 amino-acid peptide, urocortin 1, 40 amino-acids, urocortin 2, 38 amino-acids and urocortin 3, 38 amino-acids. CRF1 and CRF2 receptors are activated non-selectively by CRH and UCN. CRF2 receptors are selectively activated by UCN2 and UCN3. Binding to CRF receptors can be conducted using radioligands [125I]Tyr0-CRF or [125I]Tyr0-sauvagine with Kd values of 0.1-0.4 nM. CRF1 and CRF2 receptors are non-selectively antagonized by α-helical CRF, D-Phe-CRF-(12-41) and astressin. CRF1 receptors are selectively antagonized by small molecules NBI27914, R121919, antalarmin, CP 154,526, CP 376,395. CRF2 receptors are selectively antagonized by antisauvagine and astressin 2B.
CRF1 receptorThe CRF1 receptor, a.k.a. CRHR1, has been cloned from a variety of species ranging from fish to man [1,2,3,4,5,6,7,8,9,10,11]. The CRF1 receptor is widely expressed in the central nervous system with high levels of expression in cortex, cerebellum, hippocampus, basolateral amygdala, bed nucleus of thes stria terminalis, olfactory bulb and anterior pituitary [8,12,13]. In the periphery, CRF1 receptor mRNA is expressed at low levels in the skin, ovary, testis and adrenal gland [4,8,14].
Binding and functional studies using cell lines recombinantly or endogenously expressing CRF1 receptors revealed a distinct ligand-selective profile whereby human and ovine CRF, urocortin 1, urotensin I, and sauvagine all bind with high affinity to the mammalian CRF1 receptor and activate the cyclic AMP signaling pathway [6,15,16,17]. In contrast, urocortin 2 and urocortin 3 do not bind to or activate CRF1 receptors [18,19,20,21]. Therefore, CRF and urocortin 1 can be classified as the endogenous ligands for mammalian CRF1 receptors.
- Chen R, Lewis KA, Perrin MH, et al. Expression cloning of a human corticotropin-releasing-factor receptor. Proc Natl Acad Sci USA 1993;90:8967-71.
- Chang CP, Pearse 2nd RV, O'Connell S, et al. Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain. Neuron 1993;11:1187-95.
- Perrin MH, Donaldson CJ, Chen R, et al. Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor. Endocrinology 1993;133:3058-61.
- Vita N, Laurent P, Lefort S, et al. Primary structure and functional expression of mouse pituitary and human brain corticotrophin releasing factor receptors. FEBS Lett 1993;335:1-5.
- Yu J, Xie LY, Abou-Samra AB. Molecular cloning of a type A chicken corticotropin-releasing factor receptor with high affinity for urotensin I. Endocrinology 1996;137:192-7.
- Dautzenberg FM, Dietrich K, Palchaudhuri MR, et al. Identification of two corticotropin-releasing factor receptors from Xenopus laevis with high ligand selectivity: unusual pharmacology of the type 1 receptor. J Neurochem 1997;69:1640-9.
- Myers DA, Trinh JV, Myers TR. Structure and function of the ovine type 1 corticotropin releasing factor receptor (CRF1) and a carboxyl-terminal variant. Mol Cell Endocrinol 1998;144:21-35.
- Palchaudhuri MR, Wille S, Mevenkamp G, et al. Corticotropin-releasing factor receptor type 1 from Tupaia belangeri--cloning, functional expression and tissue distribution. Eur J Biochem 1998;258:78-84.
- Arai M, Assil IQ, Abou-Samra AB. Characterization of three corticotropin-releasing factor receptors in catfish: a novel third receptor is predominantly expressed in pituitary and urophysis. Endocrinology 2001;142:446-54.
- Pohl S, Darlison MG, Clarke WC, et al. Cloning and functional pharmacology of two corticotropin-releasing factor receptors from a teleost fish. Eur J Pharmacol 2001;430:193-202.
- Oshida Y, Ikeda Y, Chaki S, et al. Monkey corticotropin-releasing factor1 receptor: Complementary DNA cloning and pharmacological characterization. Life Sci 2004;74:1911-1924.
- Potter E, Sutton S, Donaldson C, et al. Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary. Proc Natl Acad Sci USA 1994;91:8777-81.
- Chalmers DT, Lovenberg TW, Grigoriadis DE, et al. Corticotrophin-releasing factor receptors: from molecular biology to drug design. Trends Pharmacol Sci 1996;17:166-72.
- Nappi RE, Rivest S. Stress-induced genetic expression of a selective corticotropin-releasing factor-receptor subtype within the rat ovaries: an effect dependent on the ovulatory cycle. Biol Reprod 1995;53:1417-28.
- Donaldson CJ, Sutton SW, Perrin MH, et al. Cloning and characterization of human urocortin. Endocrinology 1996;137:2167-70.
- Dautzenberg FM, Py-Lang G, Higelin J, et al. Different binding modes of amphibian and human corticotropin-releasing factor type 1 and type 2 receptors: evidence for evolutionary differences. J Pharmacol Exp Ther 2001;296:113-20.
- Perrin MH, Sutton SW, Cervini LA, et al. Comparison of an agonist, urocortin, and an antagonist, astressin, as radioligands for characterization of corticotropin-releasing factor receptors. J Pharmacol Exp Ther 1999;288:729-34.
- Lewis K, Li C, Perrin MH, et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc Natl Acad Sci USA 2001;98:7570-5.
- Reyes TM, Lewis K, Perrin MH, et al. Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc Natl Acad Sci USA 2001;98:2843-8.
- Hsu SY, Hsueh AJ. Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. Nat Med 2001;7:605-11.
- Dautzenberg FM, Gutknecht E, Van der Linden I, et al. Cell type specific calcium signaling by corticotropin-releasing factor type 1 (CRF1) and 2a (CRF2(a)) receptors: Gq coupling in human embryonic kidney 293 but not SK-N-MC neuroblastoma cells. Biochem Pharmacol 2004;68:1833-1844.
Excerpt from IUPHAR/BPS Guide to Pharmacology
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