Target type: molecularfunction
Combining with the corticotrophin-releasing factor family of ligands, including the urocortins, to initiate a change in cell activity. [PMID:12032352]
Corticotrophin-releasing factor receptor (CRFR) activity is a crucial component of the hypothalamic-pituitary-adrenal (HPA) axis, playing a central role in the body's response to stress. CRFRs are G protein-coupled receptors (GPCRs) that bind to corticotrophin-releasing factor (CRF), a neuropeptide released from the hypothalamus in response to various stressors. Upon CRF binding, the receptor undergoes conformational changes, activating its associated G protein. This activation triggers downstream signaling cascades, primarily involving the cAMP pathway and the MAPK pathway, leading to the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. ACTH then stimulates the adrenal cortex to produce and release cortisol, the primary stress hormone.
The molecular function of CRFR activity involves a series of intricate steps:
1. **Ligand Binding:** CRF binds to the extracellular domain of the CRFR, initiating a conformational change in the receptor.
2. **G Protein Coupling:** The activated receptor couples with a G protein, typically a Gs protein, which is composed of alpha, beta, and gamma subunits.
3. **Adenylate Cyclase Activation:** The activated Gs protein stimulates adenylate cyclase, an enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP).
4. **cAMP Signaling:** cAMP acts as a second messenger, activating protein kinase A (PKA) and other downstream effectors.
5. **Transcriptional Regulation:** PKA can phosphorylate and activate transcription factors, such as CREB (cAMP response element-binding protein), leading to the expression of genes involved in stress response.
6. **Calcium Signaling:** CRFR activation can also trigger calcium signaling pathways, which further contribute to stress response.
The molecular function of CRFR activity is complex and involves a tightly regulated interplay between different signaling pathways. This activity is essential for maintaining homeostasis during stress, and dysregulation of CRFR signaling can lead to various physiological and psychological disorders.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Corticotropin-releasing factor receptor 2 | A corticotropin-releasing factor receptor 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13324] | Homo sapiens (human) |
| Corticotropin-releasing factor receptor 1 | A corticotropin-releasing factor receptor 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P34998] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| hypericin | |||
| palmidrol | palmidrol: a cannabinoid receptor-inactive eCB-related molecule used as prophylactic in helping to prevent respiratory viral infection palmitoyl ethanolamide : An N-(long-chain-acyl)ethanolamine that is the ethanolamide of palmitic (hexadecanoic) acid. | endocannabinoid; N-(long-chain-acyl)ethanolamine; N-(saturated fatty acyl)ethanolamine | anti-inflammatory drug; anticonvulsant; antihypertensive agent; neuroprotective agent |
| nbi 27914 | dialkylarylamine; tertiary amino compound | ||
| antalarmin | antalarmin : A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidin-4-amine which is substituted by methyl groups at positions 2, 5, and 6, by a mesityl group at position 7, and in which the amino substituent at position 4 has been substituted by ethyl and butyl groups. It is an antagonist of corticotropin-releasing factor 1 (CRF-1) receptors (Ki = 1 nM). | pyrrolopyrimidine; tertiary amino compound | corticotropin-releasing factor receptor antagonist |
| capsaicin | ALGRX-4975: an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief capsaicinoid : A family of aromatic fatty amides produced as secondary metabolites by chilli peppers. | capsaicinoid | non-narcotic analgesic; TRPV1 agonist; voltage-gated sodium channel blocker |
| anandamide | anandamide : An N-acylethanolamine 20:4 resulting from the formal condensation of carboxy group of arachidonic acid with the amino group of ethanolamine. | endocannabinoid; N-acylethanolamine 20:4 | human blood serum metabolite; neurotransmitter; vasodilator agent |
| ssr 125543a | SSR125543: a CRF1 receptor antagonist with antidepressant-like effects | amine | |
| n-oleoylethanolamine | N-oleoylethanolamine: ceramidase inhibitor oleoyl ethanolamide : An N-(long-chain-acyl)ethanolamine that is the ethanolamide of oleic acid. The monounsaturated analogue of the endocannabinoid anandamide. | endocannabinoid; N-(long-chain-acyl)ethanolamine; N-acylethanolamine 18:1 | EC 3.5.1.23 (ceramidase) inhibitor; geroprotector; PPARalpha agonist |
| cp 154526 | |||
| ucb 35625 | UCB 35625: J-113863 is the (trans)-isomer; structure in first source | ||
| r 121919 | |||
| pexacerfont | pyrazolopyridine | ||
| 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1,5-a)pyrimidine | 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1,5-a)pyrimidine: an hCRF(1) antagonist; structure in first source | ||
| nbi-34041 | NBI-34041: high-affinity CRF1 (corticotropin-releasing factor receptor 1) receptor antagonist for attenuating elevated stress response | ||
| dmp 696 | DMP 696: a CRF(1) receptor antagonist; structure in first source | ||
| cp 154526 | CP 154526: structure in first source | ||
| gsk 561679 | NBI 77860: a CRF1 receptor antagonist; structure in first source | ||
| bms 665053 | BMS 665053: structure in first source | ||
| nitd 609 | NITD 609: an antimalarial and coccidiostat; structure in first source |