Search results for "RECEPTOR"
showing 10 items of 6990 documents
Melatonin stimulates the nonamyloidogenic processing ofβAPP through the positive transcriptional regulation of ADAM10 and ADAM17
2014
Melatonin controls many physiological functions including regulation of the circadian rhythm and clearance of free radicals and neuroprotection. Importantly, melatonin levels strongly decrease as we age and patients with Alzheimer's disease (AD) display lower melatonin than age-matched controls. Several studies have reported that melatonin can reduce aggregation and toxicity of amyloid-β peptides that are produced from the β-amyloid precursor protein (βAPP). However, whether melatonin can directly regulate the βAPP-cleaving proteases ('secretases') has not been investigated so far. In this study, we establish that melatonin stimulates the α-secretase cleavage of βAPP in cultured neuronal an…
Photo-DHEA--a functional photoreactive dehydroepiandrosterone (DHEA) analog.
2011
Abstract The steroid hormone dehydroepiandrosterone (DHEA) has beneficial effects on vascular function, survival of neurons, and fatty acid metabolism. However, a specific receptor for DHEA has not been identified to date. Here, we describe the synthesis of a photoreactive DHEA derivative (Photo-DHEA). In Photo-DHEA, typical characteristics of DHEA are conserved: (i) a “planar” tetracyclic ring system with a Δ 5 double bond, (ii) a 3β-hydroxyl group, and (iii) a keto group at C17. In cell-based assays, Photo-DHEA showed the same properties as DHEA. We conclude that Photo-DHEA is suitable for radioiodination to yield a tool for the identification of the elusive DHEA receptor.
Regulation of serotonin release from the intestinal mucosa.
1991
Summary In the mammalian intestine serotonin (5-hydroxytryptamine, 5-HT) is present in high concentrations in the enterochromaffin cells. The release of 5-HT from the intestinal mucosa is regulated by a complex pattern of neuronal and humoral inputs to the enterochromaffin cells. The enterochromaffin cells appear to be endowed with different inhibitory ( α 2 -adrenoceptors, GABA A - and GABA B -receptors, histamine H 3 -receptors, receptors for vasoactive intestinal polypeptide and somatostatin) as well as stimulatory receptors ( β -adrenoceptors, muscarine and nicotine receptors). The physiological significance of this complex system of receptors is suggested by experiments which demonstra…
Pharmacological Characterization of Melanocortin Receptors in Fish Suggests an Important Role for ACTH
2005
The melanocortin (MC) receptor subtypes have distinctive characteristic binding profiles. We found that the trout and Fugu MC4 receptors have similar affinity for alpha-MSH and beta-MSH and a much higher affinity for ACTH than does the human MC4 receptor. The Fugu MC1 and the trout and Fugu MC5 receptors also have higher affinity for ACTH-derived peptides than alpha-, beta-, or gamma-MSH. It is tempting to speculate that ACTH-derived peptides may have played an important role as "original" ligands at the MC receptors, while the specificity of the different subtypes for the alpha-, beta-, and gamma-MSH peptides may have appeared at later stages during vertebrate evolution.
Respiratory Parameters after Systemic Corticotropin-Releasing Hormone Administration
1991
Neuroanatomical studies on the distribution of corticotropin-releasing hormone (CRH) and its receptors (7) as well as physiological data suggest a regulatory function of endogenous CRH in hypothalamic and extrahypothalamic brain areas [1, 4]. Endogenous CRH acts within the endocrine hypothalamo-pituitary-adrenal axis and affects cardiovascular regulation and respiration through extrahypothalamic pathways. CRH also stimulates gluconeogenesis and release of plasma-catecholamines. Our experiments in humans also demonstrate an influence on respiration and on heart rate activity after systemic application of CRH. Respiratory parameters and heart rate were analyzed during steady-state conditions …
Standardization of a bioassay for thyrotropin receptor stimulating autoantibodies.
2015
Cell-based bioassays for functional thyroid stimulating autoantibodies (TSAb) are sensitive diagnostic tools. However, there is no bioassay available that is standardized with international reference material. We aimed to promote the standardization of the test results among laboratories that perform TSAb bioassays and calibrate TSAb levels against the second international standard (IS) 08/204 from the National Institute for Biological Standards and Control (NIBSC).Serum TSAb activity was measured with a FDA-cleared bioassay that utilizes CHO cells expressing a chimeric thyrotropin receptor (TSHR) and a c-AMP response-element-dependent luciferase. The IS was applied for calibration. TSAb re…
Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease
2021
Abstract Context We previously presented evidence that TSH receptor (TSHR)-stimulating autoantibodies (TSAbs) bind to and activate TSHRs but do not bind to IGF1 receptors (IGF1Rs). Nevertheless, we showed that IGF1Rs were involved in thyroid eye disease (TED) pathogenesis because TSAbs activated crosstalk between TSHR and IGF1R. Teprotumumab, originally generated to inhibit IGF1 binding to IGF1R, was recently approved for the treatment of TED (Tepezza). Objective To investigate the role of TSHR/IGF1R crosstalk in teprotumumab treatment of TED. Design We used orbital fibroblasts from patients with TED (TEDOFs) and measured stimulated hyaluronan (HA) secretion as a measure of orbital fibrobla…
A Novel Long-Term Graves’ Disease Animal Model Confirmed by Functional Thyrotropin Receptor Antibodies
2020
<b><i>Introduction:</i></b> A novel long-term murine model for Graves’ disease (GD) using repeated, long-term immunizations with recombinant adenovirus expressing the extracellular A-subunit of the human thyrotropin receptor (Ad-TSHR) was applied to evaluate the functional anti-TSHR-antibody (TSHR-Ab) profile. <b><i>Methods:</i></b> BALB/c mice received 7 immunizations with either 10<sup>10</sup> plaque-forming units of Ad-TSHR or control Ad-GFP. Naïve (nonimmuized native) mice were also studied. Three 3-weekly immunizations were followed by 4-weekly boosts until the 7th immunization. Blocking (TBAb) and stimulating (TSAb) TSHR-Ab …
Clinical Relevance of Thyroid-Stimulating Immunoglobulins in Graves' Ophthalmopathy
2011
Purpose Thyroid-stimulating immunoglobulins (TSIs) likely mediate Graves' ophthalmopathy (GO). The clinical relevance of these functional autoantibodies was assessed in GO. Design Cross-sectional trial. Participants A total of 108 untreated patients with GO. Methods Thyroid-stimulating immunoglobulins, assessed with a novel bioassay, bind to the thyrotropin receptor (TSHR) and transmit signals for cyclic adenosine monophosphate (cAMP)-dependent activation of luciferase gene expression. The cAMP/cAMP response element-binding protein/cAMP-regulatory element complex induces luciferase that is quantified after cell lysis. The TSI levels were correlated with activity and severity of GO and compa…
Interleukin-1β (IL-1β) Is a Modulator of Human Luteal Cell Steroidogenesis: Localization of the IL Type I System in the Corpus Luteum1
1999
The present investigation examined the effect of interleukin-1beta (IL-1beta) on progesterone production by human luteal cells and the expression and localization of the IL-1 system in the human corpus luteum (CL). Luteal cells were isolated from corpora lutea collected throughout the luteal phase. After dispersion, luteal cells were treated with a panel of monoclonal antibodies directed to leukocyte-specific molecules. The leukocytes were isolated with immunomagnetic beads. Leukocyte-free luteal cells exhibited greater steroidogenic responsiveness to hCG toward the end of the luteal phase. The treatment of mixed luteal cells (total luteal cells) with IL-1beta inhibited by 60% hCG-stimulate…