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

Corticotropin releasing factor (CRF) receptors belong to the super-family of G protein-coupled receptors. These receptors are classified into two subtypes (CRF1 and CRF2). Both receptors are positively coupled to adenylyl cyclase but they have a distinct pharmacology and distribution in brain. Two isoforms belonging to the CRF2 subtype receptors, CRF2alpha and CRF2beta, have been identified in rat and man. The neuropeptides CRF and urocortin mediate their actions through this CRF G protein-coupled receptor family. In this report, we describe the pharmacological characterization of the recently identified hCRF2, receptor. We have used radioligand binding with [125I]-tyr0-sauvagine and a gene expression assay in which the firefly luciferase gene expression is under the control of cAMP responsive elements. Association kinetics of [125I]-tyr0-sauvagine binding to the hCRF2beta receptor were monophasic while dissociation kinetics were biphasic, in agreement with the kinetics results obtained with the hCRF2alpha receptor. Saturation binding analysis revealed two affinity states in HEK 293 cells with binding parameters in accord with those determined kinetically and with parameters obtained with the hCRF2alpha receptor. A non-hydrolysable GTP analog, Gpp(NH)p, reduced the high affinity binding of [125I]-tyr0-sauvagine to both hCRF2 receptor isoforms in a similar manner. The rank order of potency of CRF agonist peptides in competition experiments was identical for both hCRF2 isoforms (urocortin > sauvagine > urotensin 1 > r/hCRF > alpha-helical CRF(9-41) > oCRF). Similarly, agonist potency was similar for the two isoforms when studied using the luciferase gene reporter system. The peptide antagonist alpha-helical CRF(9-41) exhibited a non-competitive antagonism of urocortin-stimulated luciferase expression with both hCRF2 receptor isoforms. Taken together, these results indicate that the pharmacological profiles of the CRF2 splice variants are identical. This indicates that the region of the N-terminus that varies between the receptors is probably not important in the binding of peptide CRF receptor ligands or functional activation of the receptor.
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PMID:Human CRF2 alpha and beta splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay. 1021 82

Adrenocorticotropic hormone (ACTH) and melanophore-stimulating hormone (MSH) are produced in the pars distalis and pars intermedia, respectively, throughout vertebrates. These hormones together with beta-endorphin are encoded on a single gene proopiomelanocortin (POMC) in gnathostomes, but in the sea lamprey, an agnathan, ACTH and MSH are encoded on two separate genes, proopiocortin (POC) and proopiomelanotropin (POM), respectively. Moreover, the nucleotide sequences of 5'-flanking regions of the POC and POM genes are significantly different from each other. To investigate the potential promoter activities of the POC and POM genes, we constructed promoter reporter plasmids by fusing the 5' flanking sequences (nucleotides -1151 to +31 and -2510 to +51, respectively) to a firefly luciferase gene. Transient transfection studies in AtT-20/D16v cells, which derived from a mouse pituitary tumor cell line, revealed that the 5'-flanking sequence of the POC gene did not exhibit promoter activity, whereas that of the POM gene showed the activity at high levels nearly equivalent to SV40 promoter. Analysis of a series of the 5'-deleted reporter for the POM gene in the AtT-20/D16v cells demonstrated that the 422 bp 5'-flanking sequence was sufficient for promoter activity, while the sequence from -853 to -574 may contain negatively acting regulatory elements. Because the POC and POM genes are supposed to have differentiated from a common ancestor, during evolution, the POC gene may lack essential element(s) for expression in the AtT-20/D16v cells.
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PMID:Promoter activity of sea lamprey proopiocortin and proopiomelanotropin genes in AtT-20/D16v cells. 1603 55

EtOH exposure in male rats increases corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus of the hypothalamus (PVN), a brain region responsible for coordinating stress and anxiety responses. In this study we identified the molecular mechanisms involved in mediating these effects by examining the direct effects of EtOH on CRH promoter activity in a neuronal cell line derived from the PVN (IVB). In addition, we investigated the potential interactions of EtOH and glucocorticoids on the CRH promoter by concomitantly treating cells with EtOH and the glucocorticoid receptor (GR) antagonist RU486, and by sequentially deleting GR binding sites within glucocorticoid response element (GRE) on the CRH promoter. Cells were transiently transfected with a firefly luciferase reporter construct containing 2.5 kb of the rat wild type (WT) or mutated CRH promoter. Our results showed that EtOH treatment induced a biphasic response in CRH promoter activity. EtOH exposure for 0.5 h significantly decreased promoter activity compared to vehicle treated controls, whereas promoter activity was significantly increased after 2.0 h of EtOH exposure. Treatment with RU486, or deletion of the GR binding sites 1 and 2 within the GRE, abolished the EtOH-induced increase in the promoter activity, however did not affect EtOH-induced decrease in CRH promoter activity at an earlier time point. Overall, our data suggest that alcohol exposure directly regulates CRH promoter activity by interfering with the normal feedback mechanisms of glucocorticoids mediated by GR signaling at the GRE site of the CRH promoter.
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PMID:Alcohol dysregulates corticotropin-releasing-hormone (CRH) promoter activity by interfering with the negative glucocorticoid response element (nGRE). 2203 22