Search results for "RECEPTORS"
showing 10 items of 3254 documents
Release of non-neuronal acetylcholine from the human placenta: difference to neuronal acetylcholine
2001
The synthesis and release of non-neuronal acetylcholine, a widely expressed signaling molecule, were investigated in the human placenta. This tissue is free of cholinergic neurons, i.e. a contamination of neuronal acetylcholine can be excluded. The villus showed a choline acetyltransferase (ChAT) activity of 0.65 nmol/mg protein per h and contained 500 nmol acetylcholine/g dry weight. In the absence of cholinesterase inhibitors the release of acetylcholine from isolated villus pieces amounted to 1.3 nmol/g wet weight per 10 min corresponding to a fractional release rate of 0.13% per min. The following substances did not significantly modify the release of acetylcholine: oxotremorine (1 micr…
Lack of autoreceptor mediated regulation of the spontaneous dopamine turnover in the isolated neurointermediate lobe of the rat pituitary gland in vi…
1990
Isolated neurointermediate lobes of the rat pituitary gland were incubated in Krebs-HEPES solution and the spontaneous outflow of endogenous dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous outflow of dopamine metabolites (about 1500 fmol/10 min) largely exceeded that of dopamine (about 60 fmol/10 min). Apomorphine concentration-dependently (IC50, 205 nmol/l) reduced the spontaneous outflow of the dopamine metabolites. The effect of apomorphine developed slowly and was progressive over an observation period of 70 min. After 1 h of exposure to a maximall effective concentration of apomorphine (10 mumol/l), the outflow …
The non-neuronal cholinergic system in humans: expression, function and pathophysiology.
2003
Acetylcholine, a prime example of a neurotransmitter, has been detected in bacteria, algae, protozoa, and primitive plants, indicating an extremely early appearance in the evolutionary process (about 3 billion years). In humans, acetylcholine and/or the synthesizing enzyme, choline acetyltransferase (ChAT), have been found in epithelial cells (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium), endothelial, muscle and immune cells (mononuclear cells, granulocytes, alveolar macrophages, mast cells). The widespread expression of non-neuronal acetylcholine is accompanied by the ubiquitous presence of cholinesterase and receptors (nicotinic, muscarinic). …
Primary Biliary Cholangitis management: controversies, perspectives, and daily practice implications from an expert panel
2020
Primary biliary cholangitis (PBC) is a rare progressive immune-mediated liver disease that, if not adequately treated, may culminate in end-stage disease and need for transplantation. According to current guidelines, PBC is diagnosed in the presence of antimitochondrial antibodies (AMA) or specific antinuclear antibodies, and of a cholestatic biochemical profile, while biopsy is recommended only in selected cases. All patients receive ursodeoxycholic acid (UDCA) in first line; the only registered second-line therapy is obeticholic acid (OCA) for UDCA-inadequate responders. Despite the recent advances in understanding PBC pathogenesis and developing new treatments, many grey areas remain. Si…
Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repagl…
2004
The 11 C-labeled sulfonylurea receptor 1 (SUR1) ligand (S)-2-(( 11 C)methoxy)-4-(3-methyl-1-(2-piperidine-1-yl-phenyl)- butyl-carbamoyl)-benzoic acid (( 11 C)methoxy-repaglinide) was synthesized in an overall radiochemical yield of 35% after 55 min with a radiochemical purity higher than 99%. This compound is considered for the noninvasive investigation of the SUR1 receptor status of pancreatic b-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. The specific activity was 40-70 GBq/lmol. In vitro testing of the nonradioactive methoxy-repaglinide was performed to characterize the affinity for binding to the human SUR1 isoform. Methoxy-repaglinide induce…
Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma
2004
Background In asthma T cells are characterized by an increased activation state and by reduced apoptosis. Objective Because the clinical efficacy of inhaled corticosteroids combined with long-acting β 2 -agonists has been widely demonstrated in asthma, we studied, in vitro , the effect of fluticasone propionate (FP) and salmeterol alone and in combination on the activation and apoptosis of peripheral blood T cells (PBTs), on the expression of phosphorylated nuclear factor κB inhibitor (IκBα), and on the nuclear translocation of glucocorticoid receptor (GR) in PBTs from asthmatic subjects. Methods Apoptosis was evaluated on the basis of annexin V binding, whereas the expression of caspases 8…
Estradiol, acting through estrogen receptor alpha, restores dimethylarginine dimethylaminohydrolase activity and nitric oxide production in oxLDL-tre…
2011
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase. ADMA accumulation, mainly due to a decreased dimethylarginine dimethylaminohydrolase (DDAH) activity, has been related to the development of cardiovascular diseases. We investigate whether estradiol prevents the changes induced by oxidized low density lipoprotein (oxLDL) on the DDAH/ADMA/NO pathway in human umbilical artery endothelial cells (HUAEC). HUAEC were exposed to estradiol, native LDL (nLDL), oxLDL and their combinations for 24 h. In some experiments, cells were also exposed to the unspecific estrogen receptor (ER) antagonist ICI 182780, the specific ERα antagonist MPP or specific agonists …
Mechanism of New Antipsychotic Medications
2003
Antagonism of D 2 -like dopamine receptors is the putative mechanism underlying the antipsychotic efficacy of psychotropic drugs. Positron emission tomographic studies suggest that the antipsychotic effect of dopamine receptor antagonists occurs within a therapeutic window between 60% and 80%(striatal) D 2 receptor occupancy. The incidence of extrapyramidal side effects increases above the 80% threshold. However, the novel atypical antipsychotic drug, aripiprazole, occupies up to 95% of striatal D 2 -like dopamine receptors at clinical doses, and the incidence of extrapyramidal side effects with aripiprazole is no higher than with placebo. The most likely explanation for this finding is ari…
Progressive pulmonary fibrosis is mediated by TGF-β isoform 1 but not TGF-β3
2007
Tissue repair is a well-orchestrated biological process involving numerous soluble mediators, and an imbalance between these factors may result in impaired repair and fibrosis. Transforming growth factor (TGF)-beta is a key profibrotic element in this process and it is thought that its three isoforms act in a similar way. Here, we report that TGF-beta3 administered to rat lungs using transient overexpression initiates profibrotic effects similar to those elicited by TGF-beta1, but causes less severe and progressive changes. The data suggest that TGF-beta3 does not lead to inhibition of matrix degradation in the same way as TGF-beta1, resulting in non-fibrotic tissue repair. Further, TGF-bet…
New strategies for medical management of overactive bladder in children.
2011
Purpose of review The medical treatment of children with non-neurogenic overactive bladder syndrome (OAB) is still limited to a small number of drugs approved for use in childhood according to the national regulations of each country. Recent findings Over the last few years, there were several studies on the use of antimuscarinics other than oxybutynin in children, as well as some on the use of extended release oxybutynin and tolterodine and transdermal oxybutynin. It was shown that the combination of two different anticholinergics might be a well tolerated and successful option in children with OAB refractory to monotherapy, as well as administration of a receptor-selective antimuscarinic …