Search results for "Receptor"
showing 10 items of 6990 documents
Microarray-based mutation analysis of 183 Spanish families with Usher syndrome.
2010
PURPOSE. The purpose of this study was to test the ability of the genotyping microarray for Usher syndrome (USH) to identify the mutations responsible for the disease in a cohort of 183 patients with USH. METHODS. DNA from 183 patients with Usher syndrome from the Spanish population was analyzed using a genotyping microarray containing 429 previously identified disease-associated variants in eight USH genes. Mutations detected by the array were confirmed by direct sequencing. Haplotype analysis was also performed in families carrying common Spanish mutations. RESULTS. The genotyping microarray identified 43 different variants, divided into 32 disease causative and 11 probably non-pathologic…
Progressive Endoplasmic Reticulum Stress Contributes to Hepatocarcinogenesis in Fatty Acyl-CoA Oxidase 1–Deficient Mice
2011
Fatty acyl-coenzyme A oxidase 1 (ACOX1) knockout (ACOX1(-/-)) mice manifest hepatic metabolic derangements that lead to the development of steatohepatitis, hepatocellular regeneration, spontaneous peroxisome proliferation, and hepatocellular carcinomas. Deficiency of ACOX1 results in unmetabolized substrates of this enzyme that function as biological ligands for peroxisome proliferator-activated receptor-α (PPARα) in liver. Here we demonstrate that sustained activation of PPARα in ACOX1(-/-) mouse liver by these ACOX1 substrates results in endoplasmic reticulum (ER) stress. Overexpression of transcriptional regulator p8 and its ER stress-related effectors such as the pseudokinase tribbles h…
Hypertension, diabetes mellitus, and insulin resistance: the role of intracellular magnesium.
1997
Magnesium is one of the most abundant ions present in living cells and its plasma concentration is remarkably constant in healthy subjects. Plasma and intracellular magnesium concentrations are tightly regulated by several factors. Among them, insulin seems to be one of the most important. In fact, in vitro and in vivo studies have demonstrated that insulin may modulate the shift of magnesium from extracellular to intracellular space. Intracellular magnesium concentration has also been shown to be effective on modulating insulin action (mainly oxidative glucose metabolism), offset calcium-related excitation-contraction coupling, and decrease smooth cell responsiveness to depolarizing stimul…
Effects of oxidative modifications induced by the glycation of bovine serum albumin on its structure and on cultured adipose cells
2005
Non-enzymatic glycosylation (glycation) and oxidative damages represent major research areas insofar as such modifications of proteins are frequently observed in numerous states of disease. Albumin undergoes structural and functional alterations, caused by increased glycosylation during non insulin-dependent diabetes mellitus, which is closely linked with the early occurrence of vascular complications. In this work, we first characterized structural modifications induced by the glycation of bovine serum albumin (BSA). A pathophysiological effect of glycated BSA was identified in primary cultures of human adipocytes as it induces an accumulation of oxidatively modified proteins in these cell…
Cloning of two melanocortin (MC) receptors in spiny dogfish
2004
We report the cloning and characterization of two melanocortin receptors (MCRs) from the spiny dogfish (Squalus acanthias) (Sac). Phylogenetic analysis shows that these shark receptors are orthologues of the MC3R and MC5R subtypes, sharing 65% and 70% overall amino acid identity with the human counterparts, respectively. The SacMC3R was expressed and pharmacologically characterized in HEK293 cells. The radioligand binding results show that this receptor has high affinity for adrenocorticotropic hormone (ACTH)-derived peptides while it has comparable affinity for alpha- and beta-melanocyte stimulating hormone (MSH), and slightly lower affinity for gamma-MSH when compared with the human ortho…
New Melanocortin 1 Receptor Binding Motif Based on the C-Terminal Sequence of ?-Melanocyte-Stimulating Hormone
2006
The C-terminal tripeptide of the alpha-melanocyte stimulating hormone (alpha-MSH11-13) possesses strong antiinflammatory activity without known cellular target. In order to better understand the structural requirements for function of such motif, we designed, synthesized and tested out Trp- and Tyr-containing analogues of the alpha-MSH11-13. Seven alpha-MSH11-13 analogues were synthesized and characterized for their binding to the melanocortin receptors recombinantly expressed in insect (Sf9) cells, infected with baculovirus carrying corresponding MC receptor DNA. We also tested these analogues on B16-F1 mouse melanoma cells endogenously expressing the MC1 receptor for binding and for abili…
gamma-Aminobutyric acid and cholinergic transmission in the guinea-pig ileum.
1983
1. The effects of GABA on release of acetylcholine and on contractility of the smooth muscle were studied in the myenteric plexus-longitudinal muscle preparation of the guinea pig. Acetylcholine was determined as radiolabelled transmitter from strips preloaded with 3H-choline. 2. GABA (1–300 μM) caused an increase in resting tension of smooth muscle as well as an increase in release of acetylcholine that was considerably reduced by tetrodotoxin. The facilitation by GABA of acetylcholine release exhibited a marked tachyphylaxis. The increase in muscle tension was clearly related to the increase in acetylcholine release. Muscimol (0.1–10 μM) also enhanced the release of acetylcholine. The eff…
Characterization of prejunctional muscarinic autoreceptors in the guinea-pig trachea
1991
1. The effects of ten muscarinic antagonists on electrically evoked [3H]-acetylcholine release and muscle contraction were compared in an epithelium-free preparation of the guinea-pig trachea that had been preincubated with [3H]-choline. 2. The M3-selective antagonists UH-AH 37, 4-diphenyl-acetoxy-N-piperidine methobromide and para-fluorohexahydrosiladiphenidol were more potent in reducing the contractile response than in facilitating the evoked [3H]-acetylcholine release. Hexahydrosiladiphenidol did not discriminate between pre- and postjunctional effects. The rank order of the postjunctional potencies of the ten antagonists as well as the postjunctional pA2 values obtained for hexahydrosi…
Inhibitory and excitatory muscarinic receptors modulating the release of acetylcholine from the postganglionic parasympathetic neuron of the chicken …
1992
The effects of muscarinic receptor antagonists on ACh release were studied in the absence or presence of cholinesterase (ChE) inhibition using the isolated perfused chicken heart. Presynaptic inhibitory muscarinic autoreceptor were characterized by determining the potency of various antagonists to enhance [3H]-ACh release evoked by field stimulation (3 Hz, 1 min). The order of potencies was: (±)-telenzepine > atropine > 4-DAMP > silahexocyclium > pirenzepine > hexahydro-siladifenidol > AF-DX 116. The comparison with known pA2 values for M1-, M2- and M3-receptors revealed that the presynaptic autoreceptor meets the criteria of an M1-receptor. Basal, not electrically evoked overflow of unlabe…
Choline inhibits acetylcholine release via presynaptic muscarine receptors
1981
The effect of exogenous choline on the outflow of 3H-acetylcholine evoked by field stimulation was studied on the myenteric plexus-longitudinal muscle preparation of the guinea pig. Choline at concentrations of 100 microM and higher depressed the evoked outflow of 3H-acetylcholine in a concentration-dependent manner. The EC50 for the inhibitory action was 300 microM. Scopolamine (10 nM) antagonized the effect of choline which indicates that the inhibition of 3H-acetylcholine outflow is mediated by muscarine receptors. The findings imply that choline at high concentrations does not improve cholinergic synaptic neurotransmission in tissues that are endowed with presynaptic muscarine receptors…