Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral corticotropin-releasing hormone (CRH) is an important regulator of localized inflammatory responses. The aim of this study is to define the pathological signaling pathways in which peripheral CRH receptor-mediated responses reside. We report that PECAM-1-expressing synovial membrane endothelial cells are the principal source of CRH receptor subtype 1alpha in chronically inflamed synovial tissue (ST). Analysis of ST from an early arthritis patient cohort (n = 9) established that expression of CRH-R1alpha significantly (P < 0.03) colocalized with PECAM-1 and E-selectin expression in vivo. Freshly excised ST explants released a mediator(s) that acts to promote CRH-R1alpha mRNA to levels present in inflamed human synovium (n = 8). We tested the ability of conditioned medium and individual inflammatory mediators to modulate CRH-R1alpha expression. Histamine selectively induced the expression of CRH-R1alpha, and these effects were mediated through the histamine receptor type 1. Ectopic expression of CRH-R1alpha in normal human endothelial and synoviocyte cells resulted in the induction of the orphan receptor NR4A2 through the reconstitution of cAMP/protein kinase A/cAMP response element-binding protein signaling and identified a role for CRH in modulating nuclear factor kappaB transcriptional activity. CRH enhanced the expression of nitric-oxide synthase (NOS III) to promote NO production from CRH-R1alpha-expressing cells. These data establish a role for CRH receptor-mediated responses in regulating vascular changes associated with chronic synovitis.
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PMID:A role for type 1alpha corticotropin-releasing hormone receptors in mediating local changes in chronically inflamed tissue. 1732 94

The melanocortin-1 receptor (MCIR) is a G-protein-coupled receptor expressed primarily in melanocytes and is known to play a pivotal role in the regulation of pigmentation in mammals. In humans MC1R has been found to be highly polymorphic with several functional variants associated with the phenotype of red hair color and fair skin, cutaneous UV sensitivity, and increased risk of developing melanoma and non-melanoma skin cancer. Recent evidence suggests that MC1R plays a photo-protective role in melanocytes in response to UV irradiation. Relatively few genetic targets of MC1R signaling have been identified independent of the pigmentation pathway. Here we show that MC1R signaling in B16 mouse melanoma cells and primary human melanocytes rapidly, and transiently, induces the transcription of the NR4A subfamily of orphan nuclear receptors. Furthermore, primary human melanocytes harboring homozygous RHC variant MC1R alleles exhibited an impaired induction of NR4A genes in response to the potent MC1R agonist (Nle4,D-Phe7)-alpha-melanocyte-stimulating hormone. Using small interference RNA-mediated attenuation of NR4A1 and NR4A2 expression in melanocytes, the ability to remove cyclobutane pyrimidine dimers following UV irradiation appeared to be impaired in the context of MC1R signaling. These data identify the NR4A receptor family as potential mediators of an MC1R-coordinated DNA damage response to UV exposure in melanocytic cells.
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PMID:Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells. 1829 87