Presence Of Norepinephrine Research Articles

Silica nanodots: Luminescent effects and insights for the determination of catecholamines

The effect of various catecholamines on the luminescent properties of silica nanodots (SiNDs) was studied and the new method using SiNDs that represent a promising green alternative to other analytical techniques for the determination of catecholamines has been developed. A change in spectral properties of SiNDs in the presence of catecholamines occurs, depending on the nature of the substance. Dopamine causes a decrease in the luminescence intensity of SiNDs at 445 nm whereas in the presence of norepinephrine and epinephrine a maximum appears in the luminescence spectrum of SiNDs at 500 and 510 nm, respectively. The intensity at 445 nm or the ratio of the intensities at 500 (510) nm and 445 nm can be used as analytical signals for the determination of the corresponding catecholamines. Limits of detection for dopamine, norepinephrine and epinephrine are 2, 0.06, and 0.14 µM, respectively.

Effects of Cold on the Adrenoreactivity of the Rat Superior Mesenteric Artery

In experiments on segments of the rat superior mesenteric artery (SMA) under isometric conditions, the effect of cold on the reactivity of this artery, estimated by the magnitude of the contractile reaction of its segments to noradrenaline (NA) at a concentration of 0.01–10.0 µM, as well as to electrical field stimulation (EFS) of perivascular nerves with a frequency of 3, 10 and 40 Hz in the absence and presence of NA in the medium and at a temperature of 37 oC or 25 oC was studied. Cooling was found not to change the tone of the SMA caused by NA at all the concentrations used. In the absence and presence of NA at a low concentration (0.01–0.10 µM), cooling leads to a significant decrease in the neurogenic response of the SMA at all frequencies of EFS, while in the presence of NA at a high concentration (1–10 µM), cooling has no statistically significant effect on this response. In the presence of NA at a low concentration, cooling at low EFS frequencies insignificantly, and at high frequency significantly reduces the potentiating effect of NA on neurogenic contraction of SMA. NA at a high concentration under normal temperature conditions, reduces the neurogenic contraction at all EFS frequencies, while under cooling conditions at low frequencies it has a potentiating effect, and at high EFS frequency it has a depressing effect. The results obtained show that the depressing effect of cold on the neurogenic constriction of the rat SMA, observed at low and disappearing at high concentrations of NA, as well as on the NA-evoked potentiation of the neurogenic vasoconstriction, is not associated with a decrease in the contractile effect of NA, which is the main neurotransmitter in this artery. These effects can contribute to the redistribution of blood from the surface deep into the body, thus reducing heat loss and improve thermoregulation.

Gelatin Carbon Dots Interaction with Nitrosyl Ruthenium Complex: Fluorescence Quenching and Chemiluminescence Mechanisms.

Carbon dots (CDs) exhibit luminescence, biocompatibility, and higher water solubility. This material has been developed for biological applications, specifically in bioimaging. In this work, the gelatin carbon dots (CDg) was obtained from commercial gelatin using a hydrothermal method in domestic microwave, and the suppression fluorescent mechanism were enhanced by the addition of the [RuII(bdq)(NO)(tpy)]3+ (Rubdq-NO+) complex ion. After purification through a dialysis bag, the resulting CDs (CDg) exhibit fluorescent emission at 400nm and maintained fluorescence stability in an aqueous solution (pH = 7) for 30days under 5 ◦C. Fluorescence quenching studies revealed an electrostatic interaction between the negative charge from CDg (δ = - 20mV) and the positively charged nitrosyl (NO+) ligand of the ruthenium complex (Rubdq-NO+), resulting in quenching of the CDg fluorescence due to the inner filter effects (IFE). The chemiluminescence reaction of CDg and Rubdq-NO-CDg in presence of norepinephrine (NOR) were evaluated. NOR in PBS are liable to undergo spontaneous oxidation to quinone form (NOR-quinone). CDg are believed interact with NOR-quinone and an electron transfer occur obtained CDg+ accompanied to green emission fluorescence (520nm). While for Rubdq-NO-CDg in presence of NOR, the green emission occurs accompanied by NO0 release using DAF-2 probe.

Effects of Catecholamine Stress Hormones Norepinephrine and Epinephrine on Growth, Antimicrobial Susceptibility, Biofilm Formation, and Gene Expressions of Enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) is a significant contributor to diarrhea. To determine whether ETEC-catecholamine hormone interactions contribute to the development of diarrhea, we tested the effects of catecholamine hormones acting on ETEC in vitro. The results showed that in the presence of norepinephrine (NE) and epinephrine (Epi), the growth of 9 out of 10 ETEC isolates was promoted, the MICs of more than 60% of the isolates to 6 antibiotics significantly increased, and the biofilm formation ability of 10 ETEC isolates was also promoted. In addition, NE and Epi also significantly upregulated the expression of the virulence genes feaG, estA, estB, and elt. Transcriptome analysis revealed that the expression of 290 genes was affected by NE. These data demonstrated that catecholamine hormones may augment the diarrhea caused by ETEC.

QseBC regulates in vitro and in vivo virulence of Aeromonas hydrophila in response to norepinephrine.

The inter-kingdom communication between host and pathogenic bacteria mediated by the host hormones epinephrine (Epi)/norepinephrine (NE)/autoinducer-3 (AI-3) and transduced by the bacterial two-component signal transduction system QseBC has been well demonstrated in mammalian pathogens. Aeromonas hydrophila, a common opportunistic pathogen in freshwater aquaculture, responds to NE by increased bacterial growth and enhanced virulence. However, the underlying mechanisms remain poorly understood. Our study demonstrated that deletion of qseB and qseC significantly inhibited NE-promoted growth, biofilm formation, and hemolytic activity of A. hydrophila. The adhesion ability of ΔqseB and ΔqseC to J774a.1cells was significantly decreased compared with the wild-type strain in the presence and absence of NE, whereas NE still enhanced the adhesion ability of the mutant and wild-type strains with a similar effect, suggesting that NE-enhanced cell adhesion was independent of QseBC. Moreover, QseBC did not affect the swimming and swarming motility of A. hydrophila with or without NE. Quantitative real-time PCR analyses revealed the down-regulated expression of some virulence-related genes (hly, ast, act, aerA) in each mutant compared with the wild-type strain in the presence of NE. Tilapia infection experiments indicated that deletion of qseB or qseC weakened NE-promoted virulence of A. hydrophila. In conclusion, our study suggests that NE stimulates the growth, biofilm formation, and hemolytic activity of A. hydrophila and enhances the virulence of the pathogen in fish via the QseBC system.

Multi-walled carbon nanotube/graphene oxide/poly(threonine) composite electrode for boosting electrochemical detection of paracetamol in biological samples

We developed an electrochemical sensing tool based on the electropolymerization of l-threonine (Thr) followed by the deposition of graphene oxide (GO) and multi-walled carbon nanotube (MWCNT) on the glassy carbon electrode (GCE). The surface morphological study of the proposed electrodes confirmed the formation of composites consisting of poly(Thr), MWCNT, and GO on the GCE by FE-SEM and the structural characterization of the MWCNT/GO composite was confirmed by Raman and ATR-IR analysis. The prepared electrode (MWCNT/GO/Poly(Thr)/GCE) showed high catalytic activity for paracetamol (PCT) determination in comparison to bare GCE, Poly(Thr)/GCE, and MWCNT/GO/GCE. The proposed sensor exhibited an excellent linear response of MWCNT/GO/Poly(Thr)/GCE toward PCT with a limit of detection (LOD) of 0.16 µM by differential pulse voltammetry. In the presence of norepinephrine (NEP) and folic acid (FA), the voltammetric signal of PCT was not significantly disturbed, revealing the good selectivity of the developed sensor. Moreover, the designed sensor displayed sufficient repeatability, satisfactory reproducibility, and acceptable stability. Finally, the modified sensor has been successfully applied for the detection of PCT in tablet formulation and human serum samples.

Low-interference norepinephrine signal on dopamine detection using nafion-coated boron doped diamond electrodes

The detection of dopamine in the presence of norepinephrine using nafion-coated boron doped diamond (Nafion-BDD) electrodes was presented. An increase current signal for dopamine could be observed at around 0.75 V using Nafion-BDD, while a change in the current signal of norepinephrine that appears at similar potential was not observed. This might be due to electronegativity of the norepinephrine that is not positive enough to be attracted towards the nafion membrane, albeit neutral enough to pass through the membrane and undergo electrochemical oxidation. An optimization process including accumulation time of dopamine inside the nafion layer, solution of the pH, and nafion thickness was conducted to exploit the difference electrochemical behavior between those two catecholamines at the Nafion-BDD. Using an accumulation time of 300 s, solution pH of 7, and nafion thickness of 1.1 μm, dopamine's LOD was found to be 0.966 μM. Low-interference signal of norepinephrine to the dopamine could be observed with an excellent %recovery of dopamine in 5% range when the concentration of norepinephrine was 10 times lower compared to dopamine concentration.

Adrenoceptor sub-type involvement in Ca2+ current stimulation by noradrenaline in human and rabbit atrial myocytes

Atrial fibrillation (AF) from elevated adrenergic activity may involve increased atrial L-type Ca2+ current (ICaL) by noradrenaline (NA). However, the contribution of the adrenoceptor (AR) sub-types to such ICaL-increase is poorly understood, particularly in human. We therefore investigated effects of various broad-action and sub-type-specific α- and β-AR antagonists on NA-stimulated atrial ICaL. ICaL was recorded by whole-cell-patch clamp at 37 °C in myocytes isolated enzymatically from atrial tissues from consenting patients undergoing elective cardiac surgery and from rabbits. NA markedly increased human atrial ICaL, maximally by ~ 2.5-fold, with EC75 310 nM. Propranolol (β1 + β2-AR antagonist, 0.2 microM) substantially decreased NA (310 nM)-stimulated ICaL, in human and rabbit. Phentolamine (α1 + α2-AR antagonist, 1 microM) also decreased NA-stimulated ICaL. CGP20712A (β1-AR antagonist, 0.3 microM) and prazosin (α1-AR antagonist, 0.5 microM) each decreased NA-stimulated ICaL in both species. ICI118551 (β2-AR antagonist, 0.1 microM), in the presence of NA + CGP20712A, had no significant effect on ICaL in human atrial myocytes, but increased it in rabbit. Yohimbine (α2-AR antagonist, 10 microM), with NA + prazosin, had no significant effect on human or rabbit ICaL. Stimulation of atrial ICaL by NA is mediated, based on AR sub-type antagonist responses, mainly by activating β1- and α1-ARs in both human and rabbit, with a β2-inhibitory contribution evident in rabbit, and negligible α2 involvement in either species. This improved understanding of AR sub-type contributions to noradrenergic activation of atrial ICaL could help inform future potential optimisation of pharmacological AR-antagonism strategies for inhibiting adrenergic AF.

Cholinergic signaling impairs cardiomyocyte cohesion.

Cardiac autonomic nervous system (ANS) dysregulation is a hallmark of several cardiovascular diseases. Adrenergic signaling enhanced cardiomyocyte cohesion via PKA-mediated plakoglobin phosphorylation at serine 665, referred to as positive adhesiotropy. This study investigated cholinergic regulation of cardiomyocyte cohesion using muscarinic receptor agonist carbachol (CCH). Dissociation assays, Western blot analysis, immunostaining, atomic force microscopy (AFM), immunoprecipitation, transmission electron microscopy (TEM), triton assays, and siRNA knockdown of genes were performed in either HL-1 cells or plakoglobin (PG) wild type (Jup+/+ ) and knockout (Jup-/- ) mice, which served as a model for arrhythmogenic cardiomyopathy. In HL-1 cells grown in norepinephrine (NE)-containing medium for baseline adrenergic stimulation, and murine cardiac slice cultures from Jup+/+ and Jup-/- mice CCH treatment impaired cardiomyocyte cohesion. Immunostainings and AFM experiments revealed that CCH reduced desmoglein 2 (DSG2) localization and binding at cell borders. Furthermore, CCH reduced intercalated disc plaque thickness in both Jup+/+ and Jup-/- mice, evidenced by TEM analysis. Immunoprecipitation experiments in HL-1 cells revealed no changes in DSG2 interaction with desmoplakin (DP), plakophilin 2 (PKP2), PG, and desmin (DES) after CCH treatment. However, knockdown of any of the above proteins abolished CCH-mediated loss of cardiomyocyte cohesion. Furthermore, in HL-1 cells, CCH inhibited adrenergic-stimulated ERK phosphorylation but not PG phosphorylation at serine 665. In addition, CCH activated the AKT/GSK-3β axis in the presence of NE. Our results demonstrate that cholinergic signaling antagonizes the positive effect of adrenergic signaling on cardiomyocyte cohesion and thus causes negative adhesiotropy independent of PG phosphorylation.

Cross-interactions between Norepinephrine, Methicillin-Resistant Staphylococcus aureus and Human Osteoblast Cells in Culture Conditions

Objective: The role of norepinephrine (NE) on growth, adhesion and invasion of methicillin-resistant Staphylococcus aureus (MRSA) ATTC 43300 was examined in human osteoblast (HOB) cells. The effects of NE and/or MRSA on the viability and cell death pathways of HOB cells were also investigated. Furthermore, the alterations of bacterial response to oxidative stress (H2O2) were analyzed in the presence/ absence of NE. Materials and Methods: Bacterial growth was detected spectrophotometrically. The colony counting method was examined for adhesion-invasion. The alteration of HOB cell viability was determined by methyl thiazolyl diphenyl-tetrazolium bromide (MTT) assay. The death pathways of HOB cells were examined microscopically using acridine orange-ethidium bromide dual staining and dichlorofluorescein-diacetate (DCF-DA) dye. The bacterial response to H2O2 was investigated by agar dilution. Results: The growth of bacterium was not affected in the presence of NE. Bacterial adhesion was decreased by NE (p<0.0001) while high-level NE induced invasion (p=0.013). HOB cell viability was reduced by MRSA and/or NE (p<0.001). MRSA and co-existence of MRSA and NE caused necrosis more than apoptosis in HOB cells (p<0.05). NE did not alter the bacterial response to oxidative stress. Conclusion: Norepinephrine has different effects on the biological properties of both MRSA and HOB cells.

RETRACTED: Fabrication of a novel sensor based on Cu quantum dot and SH-SiO2 nanoparticles supported on copper-based metal organic framework (Cu QD-SH-SiO2@Cu-MOF) and its application for the simultaneous determination of norepinephrine, piroxicam and epinephrine

In this research, a novel electrochemical sensor with excellent sensitivity was fabricated based on Cu quantum dot (Cu QD) and SH-SiO2 nanoparticles immobilized on copper-metal-organic frameworks (Cu-MOFs) for determining piroxicam and simultaneous determination of norepinephrine, piroxicam and epinephrine. The nanoparticles were synthesized and characterized using FT-IR, EDX, FESEM, TEM and BET, and were subsequently used to modify carbon paste electrode. Cu QD-SH-SiO2@Cu-MOF for electrode modification possesses a distinctive structure and a high conductivity that raises the electron transfer rate and enhances the performance of electrochemical sensors. Square wave voltammetry was applied to investigate the redox properties of Cu QD-SH-SiO2@Cu-MOF/CPE, voltammograms showed three distinct anodic peaks at 0.41, 0.62 and 1.06 V in the presence of norepinephrine, piroxicam, and epinephrine. Various experimental parameters including the type and pH of electrolyte and scan rate were investigated. The calibration graph was obtained over the range 0.2–34285.0 μM including three linear segments. Also, the limit of detection was calculated as 0.05 μM of piroxicam. The introduced sensor was satisfactorily utilized for electrochemical determination of norepinephrine, piroxicam, and epinephrine in real samples. The obtained results using the introduced sensor were validated by high-performance liquid chromatography and the statistical tests confirmed the good agreement of them.

Reliability of analgesia nociception index (ANI) and surgical pleth index (SPI) during episodes of bleeding - A pilot study.

Background and Aims:Analgesia Nociception Index (ANI) and Surgical Pleth Index (SPI) are measures of nociception-antinociception balance during general anaesthesia. The validity of these two monitors during autonomic changes brought about by intraoperative blood loss and noradrenaline infusion has not been studied earlier. The primary objective of the study was to determine the effect of bleeding on ANI and SPI. The secondary objective was to observe the effect of noradrenaline infusion on ANI and SPI and the correlation between ANI and SPI.Methods:In this prospective observational study, 43 patients undergoing surgery for excision of a meningioma or for traumatic brain injury were included. Heart rate, mean arterial pressure, ANI, SPI, response and state entropy were recorded every 5 min from anaesthetic induction till skin closure. ANI and SPI values before bleeding were compared with the values following bleeding. The effect of bleeding and noradrenaline on ANI and SPI were studied using linear mixed effect model.Results:Bleeding increased the values of ANI and the increase was higher in the presence of noradrenaline and it was statistically significant (P = 0.028 and 0.023). SPI was not affected by bleeding or with noradrenaline infusion. ANI and SPI had a poor negative correlation (r = - 0.01).Conclusion:Values of ANI increased significantly during episodes of intraoperative acute blood loss and with co-administration of noradrenaline. SPI seems to be more dependable when compared to ANI under such conditions.

Electrical stimulation of the splenic nerve bundle ameliorates dextran sulfate sodium-induced colitis in mice

BackgroundVagus nerve stimulation has been suggested to affect immune responses, partly through a neuronal circuit requiring sympathetic innervation of the splenic nerve bundle and norepinephrine (NE) release. Molecular and cellular mechanisms of action remain elusive. Here, we investigated the therapeutic value of this neuromodulation in inflammatory bowel disease (IBD) by applying electrical splenic nerve bundle stimulation (SpNS) in mice with dextran sulfate sodium (DSS)-induced colitis.MethodsCuff electrodes were implanted around the splenic nerve bundle in mice, whereupon mice received SpNS or sham stimulation. Stimulation was applied 6 times daily for 12 days during DSS-induced colitis. Colonic and splenic tissues were collected for transcriptional analyses by qPCR and RNA-sequencing (RNA-seq). In addition, murine and human splenocytes were stimulated with lipopolysaccharide (LPS) in the absence or presence of NE. Single-cell RNA-seq data from publicly available data sets were analyzed for expression of β-adrenergic receptors (β-ARs).ResultsColitic mice undergoing SpNS displayed reduced colon weight/length ratios and showed improved Disease Activity Index scores with reduced Tumor Necrosis Factor α mRNA expression in the colon compared with sham stimulated mice. Analyses of splenocytes from SpNS mice using RNA-seq demonstrated specific immune metabolism transcriptome profile changes in myeloid cells. Splenocytes showed expression of β-ARs in myeloid and T cells. Cytokine production was reduced by NE in mouse and human LPS-stimulated splenocytes.ConclusionsTogether, our results demonstrate that SpNS reduces clinical features of colonic inflammation in mice with DSS-induced colitis possibly by inhibiting splenic myeloid cell activation. Our data further support exploration of the clinical use of SpNS for patients with IBD.

The Role of Norepinephrine in the Regulation of Growth, Adhesion and Invasion of Pseudomonas Aeruginosa in Human Lung Carcinoma Cell Culture

Abstract Mammalian hormones are shown to affect not only regulation of mammalian homeostasis but also play roles in cross-talk between microorganisms and their hosts. In our study, the roles of norepinephrine (NE) at two different concentrations on growth alterations, adhesion - invasion of Pseudomonas aeruginosa were investigated. The effects of NE on the growth, adhesion - invasion of P. aeruginosa ATTC 27853 were examined in human lung carcinoma (A549) cell culture. We analysed two concentrations (HNE: 0.04μg/mL and LNE: 0.0017 μg/mL) of NE considering NE’s psychological levels in a healthy individual to imitate in vivo conditions of the host. Bacterial counts of growth and adhesion-invasion were examined by the colony counting method. Growth of bacterium was significantly reduced in the presence of NE at 90’ incubation (p: 0.0004 for high concentration and p: 0.0003 for low concentration); on the other hand, at 180’ minutes incubation, only low concentration reduced the growth (p˂0.0001). While adhesion was increased in the presence of low NE concentration (p: 0.013), there was no alteration in invasion of P. aeruginosa in the presence of NE (p˃0.05). Our results suggested that NE has different effects on the growth and adhesion of P. aeruginosa and these effects depend on concentration and incubation period.

Cholinergic signaling impairs cardiomyocyte cohesion

Cardiac autonomic nervous system (ANS) dysregulation is a hallmark of cardiovascular diseases such as heart failure, arrhythmias and myocardial infarction. To understand the role of ANS in cardiomyocyte cohesion, we have previously identified that adrenergic signaling enhances cardiomyocyte cohesion via PKA‐mediated plakoglobin phosphorylation at serine 665, which we termed as positive adhesiotropy. In this study, we investigated the role of parasympathetic nervous system in cardiomyocyte cohesion, using carbachol (CCH) as a cholinergic agonist that binds to the muscarinic receptors. Dissociation assays performed in HL‐1 cells, grown in norepinephrine (NE) containing medium for baseline adrenergic stimulation, and in murine cardiac slice cultures from wild type (wt) and plakoglobin (Pg) knockout (Jup‐/‐) mice revealed an impaired cardiomyocyte cohesion after CCH treatment. Electron microscopy revealed that CCH reduced intercalated disc plaque thickness in both wt and Jup‐/‐mice. Immunostaining and atomic force microscopy in HL‐1 cells demonstrated that CCH reduced desmoglein 2 (Dsg2) localization and binding at cell borders. Immunoprecipitation showed no alterations in the interaction of Dsg2, desmoplakin, plakophilin 2 and Pg after CCH treatment. Nevertheless, knockdown of any of the above genes abrogated the loss of cardiomyocyte cohesion in response to CCH. In HL‐1 cells, CCH inhibited ERK phosphorylation but not Pg phosphorylation at serine 665 induced by forskolin/rolipram (FR) combination used for adrenergic stimulation. In addition, CCH activated the AKT/GSK‐3β axis in the presence of NE. In conclusion, our results demonstrate that cholinergic signaling antagonizes the positive effect of adrenergic signaling on cardiomyocyte cohesion and thus causes negative adhesiotropy, which is independent of Pg phosphorylation.

A novel red fluorescence dopamine biosensor selectively detects dopamine in the presence of norepinephrine in vitro

Dopamine (DA) and norepinephrine (NE) are pivotal neuromodulators that regulate a broad range of brain functions, often in concert. Despite their physiological importance, untangling the relationship between DA and NE in the fine control of output function is currently challenging, primarily due to a lack of techniques to allow the observation of spatiotemporal dynamics with sufficiently high selectivity. Although genetically encoded fluorescent biosensors have been developed to detect DA, their poor selectivity prevents distinguishing DA from NE. Here, we report the development of a red fluorescent genetically encoded GPCR (G protein-coupled receptor)-activation reporter for DA termed ‘R-GenGAR-DA’. More specifically, a circular permutated red fluorescent protein (cpmApple) was replaced by the third intracellular loop of human DA receptor D1 (DRD1) followed by the screening of mutants within the linkers between DRD1 and cpmApple. We developed two variants: R-GenGAR-DA1.1, which brightened following DA stimulation, and R-GenGAR-DA1.2, which dimmed. R-GenGAR-DA1.2 demonstrated a reasonable dynamic range (ΔF/F0 = − 43%), DA affinity (EC50 = 0.92 µM) and high selectivity for DA over NE (66-fold) in HeLa cells. Taking advantage of the high selectivity of R-GenGAR-DA1.2, we monitored DA in presence of NE using dual-color fluorescence live imaging, combined with the green-NE biosensor GRABNE1m, which has high selectivity for NE over DA (> 350-fold) in HeLa cells and hippocampal neurons grown from primary culture. Thus, this is a first step toward the multiplex imaging of these neurotransmitters in, for example, freely moving animals, which will provide new opportunities to advance our understanding of the high spatiotemporal dynamics of DA and NE in normal and abnormal brain function.

Paradoxical effects of acidosis on the noradrenaline-induced and neurogenic constriction of the rat tail artery at low temperatures.

Although vasodilatation evoked by acidosis at normal body temperature is well known, the reports regarding effect of acidosis on the reactivity of the isolated arteries at low temperatures are nonexistent. This study tested the hypothesis that the inhibitory effect of acidosis on the neurogenic vasoconstriction may be increased by cooling. Using wire myography, we recorded the neurogenic contraction of the rat tail artery segments to the electrical field stimulation in the absence and in the presence of 0.03-10.0 µmol/L noradrenaline. The experiments were conducted at 37 °C or 25 °C and pH 7.4 or 6.6 which was decreased by means of CO2. Noradrenaline at concentration of 0.03-0.1 µmol/L significantly potentiated the neurogenic vasoconstriction at 25 °C, and the potentiation was not inhibited by acidosis. Contrary to our hypothesis, acidosis at a low temperature did not affect the noradrenaline-induced tone and significantly increased the neurogenic contraction of the artery segments in the absence and presence of noradrenaline. These effects of acidosis were partly dependent on the endothelium and L-type Ca2+ channels activation. The phenomenon described for the first time might be of importance for the reduction in the heat loss by virtue of decrease in the subcutaneous blood flow at low ambient temperatures.

Sulphur nanodots decorated graphene oxide nanocomposite for electrochemical determination of norepinephrine in presence and absence of 4-aminophenol, acetaminophen and tryptophan

Abstract The work reports the use of sulphur nanodots grown on graphene oxide (nS@GO) for detection of norepinephrine in presence and absence of 4-aminophenol, acetaminophen and tryptophan. The nS@GO was synthesized by one-pot method using CS2 as sulphur source using dimethylformamide (DMF) as solvent. The synthesized nanocomposite material was used for sensor application by drop-casting nS@GO (dispersed in DMF) over glassy carbon electrode. The formation of nanocomposite was confirmed using several physical characterization techniques i.e. XRD technique, Raman spectroscopy, SEM and TEM and electrochemically using cyclic voltammetry and electrochemical impedance spectroscopy. Differential pulse anodic stripping voltammetry technique was applied for quantitative determination of norepinephrine in presence and absence of 4-aminophenol, acetaminophen and tryptophan. Electrochemical impedance spectroscopy and chronoamperometry were also employed for quantitative analysis of norepinephrine. The electrochemical studies results reveal that the nS@GO based electrochemical sensor exhibits a linear response for norepinephrine in range of 0.5 to 800 μM (in absence) and 0.5–110 μM (in presence of other analytes) with sensitivities 4.986 μAμM−1cm−2 and 0.407 μAμM−1cm−2 their respective detection limit were found to be 0.26 and 0.26 μM. The nanocomposite modified electrode response was also effectively tested in real samples without any cross reactivity.

Attenuation of inward rectifier potassium current contributes to the α1-adrenergic receptor-induced proarrhythmicity in the caval vein myocardium.

This study is aimed at investigation of electrophysiological effects of α1-adrenoreceptor (α1-AR) stimulation in the rat superior vena cava (SVC) myocardium, which is one of the sources of proarrhythmic activity. α1-ARs agonists (phenylephrine-PHE or norepinephrine in presence of atenolol-NE+ATL) were applied to SVC and atrial tissue preparations or isolated cardiomyocytes, which were examined using optical mapping, glass microelectrodes or whole-cell patch clamp. α1-ARs distribution was evaluated using immunofluorescence. Kir2.X mRNA and protein level were estimated using RT-PCR and Western blotting. PHE or NE+ATL application caused a significant suppression of the conduction velocity (CV) of excitation and inexcitability in SVC, an increase in the duration of electrically evoked action potentials (APs), a decrease in the maximum upstroke velocity (dV/dtmax ) and depolarization of the resting membrane potential (RMP) in SVC to a greater extent than in atria. The effects induced by α1-ARs activation in SVC were attenuated by protein kinase C inhibition (PKC). The whole-cell patch clamp revealed PHE-induced suppression of outward component of IK1 inward rectifier current in isolated SVC, but not atrial myocytes. These effects can be mediated by α1A subtype of α-ARs found in abundance in rat SVC. The basal IK1 level in SVC was much lower than in atria as a result of the weaker expression of Kir2.2 channels. Therefore, the reduced density of IK1 in rat SVC cardiomyocytes and sensitivity of this current to α1A-AR stimulation via PKC-dependent pathways might lead to proarrhythmic conduction in SVC myocardium by inducing RMP depolarization, AP prolongation, CV and dV/dtmax decrease.

Noradrenergic Activity in the Olfactory Bulb Is a Key Element for the Stability of Olfactory Memory.

Memory stability is essential for animal survival when environment and behavioral state change over short or long time spans. The stability of a memory can be expressed by its duration, its perseverance when conditions change as well as its specificity to the learned stimulus. Using optogenetic and pharmacological manipulations in male mice, we show that the presence of noradrenaline in the olfactory bulb during acquisition renders olfactory memories more stable. We show that while inhibition of noradrenaline transmission during an odor-reward acquisition has no acute effects, it alters perseverance, duration, and specificity of the memory. We use a computational approach to propose a proof of concept model showing that a single, simple network effect of noradrenaline on olfactory bulb dynamics can underlie these seemingly different behavioral effects. Our results show that acute changes in network dynamics can have long-term effects that extend beyond the network that was manipulated.SIGNIFICANCE STATEMENT Olfaction guides the behavior of animals. For successful survival, animals have to remember previously learned information and at the same time be able to acquire new memories. We show here that noradrenaline in the olfactory bulb, the first cortical relay of the olfactory information, is important for creating stable and specific olfactory memories. Memory stability, as expressed in perseverance, duration and specificity of the memory, is enhanced when noradrenergic inputs to the olfactory bulb are unaltered. We show that, computationally, our diverse behavioral results can be ascribed to noradrenaline-driven changes in neural dynamics. These results shed light on how very temporary changes in neuromodulation can have a variety of long-lasting effects on neural processing and behavior.