Search results for "Ephrin"
showing 10 items of 345 documents
Brunner syndrome associated MAOA dysfunction in human dopaminergic neurons results in NMDAR hyperfunction and increased network activity
2020
AbstractBackgroundMonoamine neurotransmitter abundance affects motor control, emotion, and cognitive function and is regulated by monoamine oxidases. Amongst these, monoamine oxidase A (MAOA) catalyzes the degradation of dopamine, norepinephrine, and serotonin into their inactive metabolites. Loss-of-function mutations in the X-linked MAOA gene cause Brunner syndrome, which is characterized by various forms of impulsivity, maladaptive externalizing behavior, and mild intellectual disability. Impaired MAOA activity in individuals with Brunner syndrome results in bioamine aberration, but it is currently unknown how this affects neuronal function.MethodsWe generated human induced pluripotent s…
Linoleic acid induces calcium signaling, Src kinase phosphorylation, and neurotransmitter release in mouse CD36-positive gustatory cells.
2008
We have recently demonstrated that the cells expressing CD36, localized apically on the taste buds of mouse lingual circumvallate papillae, act as gustatory cells. In the present study we isolated these CD36-positive cells from mouse circumvallate papillae and investigated intracellular signaling events, triggered by a long-chain polyunsaturated fatty acid, i.e. linoleic acid (LA). LA induced increases in free intracellular calcium concentrations, [Ca(2+)](i), by recruiting calcium from endoplasmic reticulum pool via inositol 1,4,5-triphosphate production followed by calcium influx via opening of store-operated calcium (SOC) channels. LA also induced phosphorylation of Src-protein-tyrosine …
Dibutyryl cyclic AMP and adrenaline increase contractile force and 45Ca uptake in mammalian cardiac muscle
1973
The effects of dibutyryl cyclic AMP (DB-AMP; 10−3M) and adrenaline (2.2×10−6 M) on contractile force, 45Ca uptake, and total myocardial Ca concentration were investigated in electrically driven left auricles isolated from rat hearts. The experiments were performed at an extracellular Ca concentration of 0.45 mM and at low frequency of stimulation (15 beats/min). 45Ca exposure was 5 min. Under the conditions used, both drugs increased contractile force and enhanced 45Ca uptake (expressed as relative specific activity) by about 30% (DB-AMP) and 40% (adrenaline), respectively. Thus, the results provide evidence that the effects of adrenaline on 45Ca uptake in mammalian cardiac muscle can be mi…
Tetanus Toxin Inhibits Neuroexocytosis Even When Its Zn2+-dependent Protease Activity Is Removed
1995
Tetanus toxin (TeTX) is a dichain protein that blocks neuroexocytosis, an action attributed previously to Zn(2+)-dependent proteolysis of synaptobrevin (Sbr) by its light chain (LC). Herein, its cleavage of Sbr in rat cerebrocortical synaptosomes was shown to be minimized by captopril, an inhibitor of certain metalloendoproteases, whereas this agent only marginally antagonized the inhibition of noradrenaline release, implicating a second action of the toxin. This hypothesis was proven by preparing three mutants (H233A, E234A, H237A) of the LC lacking the ability to cleave Sbr and reconstituting them with native heavy chain. The resultant dichains were found to block synaptosomal transmitter…
A Colorimetric Probe for the Selective Detection of Norepinephrine Based on a Double Molecular Recognition with Functionalized Gold Nanoparticles
2019
[EN] A simple colorimetric probe for the selective and sensitive detection of neurotransmitter norepinephrine (NE), an important biomarker in the detection of tumors such as pheochromocytoma and paraganglioma, is described. The sensing strategy is based on the use of spherical gold nanoparticles functionalized with benzaldehyde and boronic acid-terminated moieties. A double molecular recognition involving on one hand the aromatic aldehyde and the aminoalcohol group of NE, and on the other hand the boronic acid and the catechol moiety of the neurotransmitter, results in analyte triggered aggregation of the gold nanoparticles, leading to a bathochromic shift of the SPR band in the UV-vis spec…
Alcohol-Mediated Renal Sympathetic Neurolysis for the Treatment of Hypertension: The Peregrine™ Infusion Catheter.
2020
Renal sympathetic denervation using conventional non-irrigated radiofrequency catheters has potential technical shortcomings, including limited penetration depth and incomplete circumferential nerve damage, potentially impacting therapeutic efficacy. Against this background, second generation multi-electrode, radiofrequency and ultrasound renal denervation systems have been developed to provide more consistent circumferential nerve ablation. Irrigated catheters may allow deeper penetration while minimizing arterial injury. In this context, catheter-based chemical denervation, with selective infusion of alcohol, a potent neurolytic agent, into the perivascular space, may minimize endothelial…
Comparative analysis of virtual screening approaches in the search for novel EphA2 receptor antagonists
2015
The EphA2 receptor and its ephrin-A1 ligand form a key cell communication system, which has been found overexpressed in many cancer types and involved in tumor growth. Recent medicinal chemistry efforts have identified bile acid derivatives as low micromolar binders of the EphA2 receptor. However, these compounds suffer from poor physicochemical properties, hampering their use in vivo. The identification of compounds able to disrupt the EphA2-ephrin-A1 complex lacking the bile acid scaffold may lead to new pharmacological tools suitable for in vivo studies. To identify the most promising virtual screening (VS) protocol aimed at finding novel EphA2 antagonists, we investigated the ability of…
Hypothalamic S-Nitrosylation Contributes to the Counter-Regulatory Response Impairment following Recurrent Hypoglycemia
2013
http://www.ncbi.nlm.nih.gov/pubmed/23894333; International audience; AIMS: Hypoglycemia is a severe side effect of intensive insulin therapy. Recurrent hypoglycemia (RH) impairs the counter-regulatory response (CRR) which restores euglycemia. During hypoglycemia, ventromedial hypothalamus (VMH) production of nitric oxide (NO) and activation of its receptor soluble guanylyl cyclase (sGC) are critical for the CRR. Hypoglycemia also increases brain reactive oxygen species (ROS) production. NO production in the presence of ROS causes protein S-nitrosylation. S-nitrosylation of sGC impairs its function and induces desensitization to NO. We hypothesized that during hypoglycemia, the interaction b…
Description of the response of a new multi-parametric brain sensor to physiological and pathophysiological challenges in the cortex of juvenile pigs
2014
AIM Monitoring of intracranial pressure (ICP), local cerebral blood flow (CBF) and oxygen is part of modern intensive critical care medicine. Preclinical evaluation of newly developed catheters that should monitor several parameters simultaneously is reported poorly in the literature. The goal of our study was (1) to evaluate a new multi-parametric sensor in brain tissue and (2) to establish a testing protocol using pathophysiological challenges that target measured parameters of the sensor and autoregulatory boundaries and could be used as preclinical standard protocol in future studies. MATERIAL AND METHODS We describe data from 12 new multi-parametric brain sensors (MPBS) that were impla…
EphrinB2 controls vessel pruning through STAT1-JNK3 signalling
2014
Angiogenesis produces primitive vascular networks that need pruning to yield hierarchically organized and functional vessels. Despite the critical importance of vessel pruning to vessel patterning and function, the mechanisms regulating this process are not clear. Here we show that EphrinB2, a well-known player in angiogenesis, is an essential regulator of endothelial cell death and vessel pruning. This regulation depends upon phosphotyrosine-EphrinB2 signalling repressing c-jun N-terminal kinase 3 activity via STAT1. JNK3 activation causes endothelial cell death. In the absence of JNK3, hyaloid vessel physiological pruning is impaired, associated with abnormal persistence of hyaloid vessel…