Search results for "G-protein-coupled receptor"
showing 10 items of 20 documents
Metabolite Sensing GPCRs: Promising Therapeutic Targets for Cancer Treatment?
2020
G-protein-coupled receptors constitute the most diverse and largest receptor family in the human genome, with approximately 800 different members identified. Given the well-known metabolic alterations in cancer development, we will focus specifically in the 19 G-protein-coupled receptors (GPCRs), which can be selectively activated by metabolites. These metabolite sensing GPCRs control crucial processes, such as cell proliferation, differentiation, migration, and survival after their activation. In the present review, we will describe the main functions of these metabolite sensing GPCRs and shed light on the benefits of their potential use as possible pharmacological targets for cancer treat…
Mitochondrial G protein coupled receptor kinase 2 regulates proinflammatory responses in macrophages.
2013
G-protein-coupled receptor kinase 2 (GRK2) levels are elevated in inflammation but its role is not clear yet. Here we show that GRK2 expression is dependent on NFκB transcriptional activity. In macrophages, LPS induces GRK2 accumulation in mitochondria increasing biogenesis. The overexpression of the carboxy-terminal domain of GRK2 (βARK-ct), known to displace GRK2 from plasma membranes, in macrophages induces earlier localization of GRK2 in mitochondria in response to LPS leading to increased mt-DNA transcription, reduced ROS production and cytokines expression. Our study shows the relevance of GRK2 subcellular localization in macrophage’s biology and its potential therapeutic properties i…
Rapid cloning of cDNA ends polymerase chain reaction of G-protein-coupled receptor kinase 6: an improved method to determine 5′- and 3′-cDNA ends
1999
Abstract Rapid cloning of 5′- and 3′-cDNA ends polymerase chain reaction (5′-/3′-RACE-PCR) is useful to determine unknown 5′- and 3′-cDNA termini. Even if the method can yield complete cDNA sequences within a couple of days, the RACE procedure bears some characteristic traps and often results in amplification of unspecific PCR-products. Here we used improved 5′- and 3′-RACE-PCR protocols to obtain the complete cDNA sequence of the G-protein-coupled receptor kinase 6 (GRK6) from a rat brain cDNA library. The use of an anchored oligo-(dT) 16 -V-primer in the cDNA synthesis, the addition of single-sided PCR steps prior to the RACE-PCRs and the optimization of the dA-tailing reaction conditions…
beta-Adrenoceptor and GRK3 expression in human lymphocytes is related to blood pressure and urinary albumin excretion.
2010
31 p., figuras, abreviaturas y bibliografía
Evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system.
2015
The ascending midbrain 5-HT neurons known to contain 5-HT1A autoreceptors may be dysregulated in depression due to a reduced trophic support. With in situ proximity ligation assay (PLA) and supported by co-location of the FGFR1 and 5-HT1A immunoreactivities in midbrain raphe 5-HT cells, evidence for the existence of FGFR1–5-HT1A heteroreceptor complexes were obtained in the dorsal and median raphe nuclei of the Sprague–Dawley rat. Their existence in the rat medullary raphe RN33B cell cultures was also established. After combined FGF-2 and 8-OH-DPAT treatment, a marked and significant increase in PLA positive clusters was found in the RN33B cells. Similar results were reached upon coactivati…
Identification of calcium sensing receptor (CaSR) mRNA-expressing cells in normal and injured rat brain
2009
Calcium sensing receptor (CaSR), isolated for the first time from bovine and human parathyroid, is a G-protein-coupled receptors that has been involved in diverse physiological functions. At present a complete in vivo work on the identification of CaSR mRNA-expressing cells in the adult brain lacks and this investigation was undertaken in order to acquire more information on cell type expressing CaSR mRNA in the rat brain and to analyse for the first time its expression in different experimental models of brain injury. The expression of CaSR mRNAs was found mainly in scattered cells throughout almost all the brain regions. A double labeling analysis showed a colocalization of CaSR mRNA expr…
Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity
2020
Mutating the side-chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half-life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioisosters can be exploited not only to enhance the proteolytic stability of parent peptides, but also to tune its receptor subtype selectivity. Towards this end, four [Y]6-Angiotensin II analogues are synthesized where amide bonds have been replaced by 1,4-disubstituted 1,2,3-triazole isosteres in four different backbone locations. All the analogues possessed enhanced stability in human plasma in comparison with the parent peptide, whereas only two of them a…
Cloning of a novel putative G-protein-coupled receptor (NLR) which is expressed in neuronal and lymphatic tissue.
1993
AbstractA novel G-protein-coupled receptor was isolated from mouse and rat neuronal and lymphatic tissues. The amino acid sequence of the rat receptor (rNLR) shows an overall homology of 80% to a recently cloned receptor from Burkitt's lymphoma cells (BLR1) which is exclusively expressed in lymphatic tissues [(1992) Eur. J. Immunol. 22, 2795]. Much less homology between rNLR and BLR1 was observed at the N-terminus (about 40%), whereas rNLR and the mouse homologue mNLR show 92% amino acid identity. Northern blot analysis of NLR revealed a predominant 5.5 kb mRNA species in various brain regions and neuronal cell lines, whereas in the spleen a 3 kb transcript is predominant. This distribution…
The impact of alpha1-adrenoceptors up-regulation accompanied by the impairment of beta-adrenergic vasodilatation in hypertension
2008
9 pages, 7 figures, 3 tables.-- PMID: 19060223 [PubMed]
Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2
2012
Tumor vessel dysfunction is a pivotal event in cancer progression. Using an in vivo neovascularization model, we identified G protein–coupled receptor kinase 2 (GRK2) as a key angiogenesis regulator. An impaired angiogenic response involving immature vessels was observed in mice hemizygous for Grk2 or in animals with endothelium-specific Grk2 silencing. ECs isolated from these animals displayed intrinsic alterations in migration, TGF-β signaling, and formation of tubular networks. Remarkably, an altered pattern of vessel growth and maturation was detected in postnatal retinas from endothelium-specific Grk2 knockout animals. Mouse embryos with systemic or endothelium-selective Grk2 ablation …