Molecular Identification and Analysis of a Novel Human Corticotropin-Releasing Factor (CRF) Receptor: The CRF2γ Receptor

Kostich, Walter; Chen, Airu; Sperle, Karen; Largent, Brian L.

doi:10.1210/mend.12.8.0145

Cited by 109 publications

(56 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These two receptor subtypes have different physiological functions and are distributed in the brain, pituitary, and various peripheral tissues [3,4,[8][9][10][11]. CRHR-1 has four splice variants (1a, 1b, 2a, and C) and CRHR-2 has three splice variants (a, b, and c), and these receptor subtypes are thought to have different actions [12,13]. CRHR-2 is important for stress-coping responses, including dearousal, sustained hypophagia, and reduced blood pressure during the recovery phase of stress response, and for avoiding damage incurred by excessive exposure to the ''fight or flight'' responses initiated by the activation of pituitary CRHR-1 [14,15].…”

Section: Introductionmentioning

confidence: 99%

Effects of corticotropin-releasing hormone and stresscopin on vascular endothelial growth factor mRNA expression in cultured early human extravillous trophoblasts

Wakahashi

Nakabayashi

Maruo

et al. 2008

Endocr

View full text Add to dashboard Cite

Corticotropin-releasing hormone (CRH) takes a role in the regulation of the onset of parturition. Stresscopin (SCP) is a high affinity ligand for CRH receptor (CRHR)-2. CRHR-2 inhibits VEGF-induced neovascularization. In the present study, we investigated the effects of CRH and SCP on VEGF expression in early placental extravillous trophoblasts (EVTs). Isolation and culture of trophoblasts differentiating into EVTs were performed by the enzymatic digestion of anchoring early placental villi. The presence of CRH, SCP, CRHR-1, and CRHR-2 in cultured EVTs was examined by RT-PCR and immunocytochemistry. The effects of CRH and SCP on VEGF mRNA levels in cultured EVTs were assessed by real-time RT-PCR. CRH, SCP, CRHR-1, and CRHR-2 were expressed in cultured EVTs at mRNA and protein levels. Treatment with either 100 nM CRH or 100 nM SCP for 24 h decreased VEGF mRNA levels in cultured EVTs. The CRH- and SCP-induced decrease in VEGF mRNA levels was counteracted by the concomitant treatment with CRHR-2 antagonist antisauvagine-30, but not with CRHR-1 antagonist antalarmin. We demonstrated that CRH and SCP inhibited VEGF mRNA expression in cultured EVTs through the interaction with CRHR-2, suggesting that CRH and SCP may inhibit angiogenesis during early placentation.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of corticotropin-releasing hormone and stresscopin on vascular endothelial growth factor mRNA expression in cultured early human extravillous trophoblasts

Wakahashi

Nakabayashi

Maruo

et al. 2008

Endocr

View full text Add to dashboard Cite

show abstract

“…Splice variants containing only the extracellular region of Gprotein-coupled receptors have been reported (17)(18)(19)(33)(34)(35)(36)(37)(38)(39). In the majority of cases, these proteins act as binding, nonsignaling molecules also referred to as decoy receptors.…”

mentioning

confidence: 99%

A soluble mouse brain splice variant of type 2α corticotropin-releasing factor (CRF) receptor binds ligands and modulates their activity

Chen

Perrin²,

DiGruccio³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Peptides of the corticotropin-releasing factor (CRF) family signal through the activation of two receptors, CRF receptor type 1 (CRFR1) and type 2 (CRFR2), both of which exist as multiple splice variants. We have identified a cDNA from mouse brain encoding a splice variant, soluble CRFR2␣ (sCRFR2␣), in which exon 6 is deleted from the gene encoding CRFR2␣. Translation of this isoform produces a predicted 143-aa soluble protein. The translated protein includes a majority of the first extracellular domain of the CRFR2␣ followed by a unique 38-aa hydrophilic C terminus resulting from a frame shift produced by deletion of exon 6. By using RT-PCR and Southern hybridization, the relative mRNA expression levels of full-length (seven transmembrane domains) CRFR2␣ and the soluble form (sCRFR2␣) in the mouse brain were measured with a single reaction. The results demonstrate high levels of expression of sCRFR2␣ in the olfactory bulb, cortex, and midbrain regions. A rabbit antiserum raised against a synthetic peptide fragment encoding the unique C terminus revealed specific sCRFR2␣ immunoreactivity in mouse brain slices by immunohistochemistry and in extracts of brain regions by RIA. Interestingly, the sCRFR2␣ immunoreactivity distribution closely approximated that of CRFR1 expression in rodent brain. A protein corresponding to sCRFR2␣, expressed and purified from either mammalian or bacterial cell systems, binds several CRF family ligands with low nanomolar affinities. Furthermore, the purified sCRFR2␣ protein inhibits cellular responses to CRF and urocortin 1. These data support a potential role of the sCRFR2␣ protein as a possible biological modulator of CRF family ligands.urocortins ͉ binding protein ͉ decoy receptor T he hypothalamic hypophysiotropic peptide corticotropin releasing factor (CRF), originally isolated from the hypothalamus (1), plays an important role in the regulation of the hypothalamopituitary-adrenal axis under basal and stress conditions (2, 3). Furthermore, CRF acts to integrate endocrine, autonomic and behavioral responses to stressors (2-4). The mammalian CRF peptide family comprises urocortin (Ucn) 1 (5) and the peptides Ucn 2 and Ucn 3, which are also known as stresscopin-related peptide (6, 7) and stresscopin (7, 8), respectively.The effects of CRF-related peptides are mediated through the activation of two high-affinity membrane receptors, CRF receptors (CRFRs) 1 (9-11) and 2 (12-16), which belong to the B1 subfamily of seven-transmembrane-domain receptors that signal by coupling to G proteins. One functional variant of the CRFR1 gene is expressed in humans and rodents, along with several nonfunctional variants, which are produced by differential splicing of various exons (17,18). The CRFR2 has three functional splice variants in human (␣, ␤, and ␥) and two rodent variants (␣ and ␤) that are produced by the use of alternate 5Ј exons (12-16, 18, 19).CRFR1 mRNA is widely expressed in mammalian brain and pituitary, with high levels found in the anterior pituitary, cerebral cortex, cerebellum, am...

show abstract

“…This receptor displays high affinity for CRF, and is positively linked to adenylate cyclase (10 -12). The second receptor, termed CRF 2 , has three splice variants (CRF 2 ␣, CRF 2 ␤ and CRF 2 ␥) (13,14). These splice variants are also members of a distinct family of seven transmembrane domain receptors.…”

mentioning

confidence: 99%

Localization and Characterization of a Short Isoform of the Corticotropin-Releasing Factor Receptor Type 2α (CRF2α-tr) in the Rat Brain

Miyata

Shiota

Chaki

et al. 2001

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Molecular Identification and Analysis of a Novel Human Corticotropin-Releasing Factor (CRF) Receptor: The CRF2γ Receptor

Cited by 109 publications

References 22 publications

Effects of corticotropin-releasing hormone and stresscopin on vascular endothelial growth factor mRNA expression in cultured early human extravillous trophoblasts

Effects of corticotropin-releasing hormone and stresscopin on vascular endothelial growth factor mRNA expression in cultured early human extravillous trophoblasts

A soluble mouse brain splice variant of type 2α corticotropin-releasing factor (CRF) receptor binds ligands and modulates their activity

Localization and Characterization of a Short Isoform of the Corticotropin-Releasing Factor Receptor Type 2α (CRF2α-tr) in the Rat Brain

Contact Info

Product

Resources

About