Block of Voltage-Gated Sodium Channels by Aripiprazole in a State-Dependent Manner.

Aripiprazole is an atypical antipsychotic drug, which is prescribed for many psychiatric diseases such as schizophrenia and mania in bipolar disorder. It primarily acts as an agonist of dopaminergic and other G-protein coupled receptors. So far, an interaction with ligand- or voltage-gated ion channels has been classified as weak.

Modulation of Neutrophil Activity by Soluble Complement Cleavage Products-An In-Depth Analysis.

The cellular and fluid phase-innate immune responses of many diseases predominantly involve activated neutrophil granulocytes and complement factors. However, a comparative systematic analysis of the early impact of key soluble complement cleavage products, including anaphylatoxins, on neutrophil granulocyte function is lacking. Neutrophil activity was monitored by flow cytometry regarding cellular (electro-)physiology, cellular activity, and changes in the surface expression of activation markers.

Simultaneous Measurement of Changes in Neutrophil Granulocyte Membrane Potential, Intracellular pH, and Cell Size by Multiparametric Flow Cytometry.

Neutrophils provide rapid and efficient defense mechanisms against invading pathogens. Upon stimulation with proinflammatory mediators, including complement factors and bacterial peptides, neutrophils respond with changes in their membrane potential, intracellular pH, and cellular size. This study provides an approach to quantify these important changes simultaneously using multiparametric flow cytometry, thereby revealing a typical sequence of neutrophil activation consisting of depolarization, alkalization, and increase in cellular size.

Activation of Neutrophil Granulocytes by Platelet-Activating Factor Is Impaired During Experimental Sepsis.

Platelet-activating factor (PAF) is an important mediator of the systemic inflammatory response. In the case of sepsis, proper activation and function of neutrophils as the first line of cellular defense are based on a well-balanced physiological response. However, little is known about the role of PAF in cellular changes of neutrophils during sepsis.

Block of Voltage-Gated Sodium Channels by Atomoxetine in a State- and Use-dependent Manner.

Atomoxetine, a neuroactive drug, is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). It is primarily known as a high affinity blocker of the noradrenaline transporter, whereby its application leads to an increased level of the corresponding neurotransmitter in different brain regions. However, the concentrations used to obtain clinical effects are much higher than those which are required to block the transporter system.

Blocking distinct interactions between Glioblastoma cells and their tissue microenvironment: A novel multi-targeted therapeutic approach.

Due to the highly invasive nature of Glioblastoma (GB), complete surgical resection is not feasible, while motile tumour cells are often associated with several specific brain structures that enhance treatment-resistance. Here, we investigate the therapeutic potential of Disulfiram and Carbenoxolone, that inhibit two distinct interactions between GB and the brain tissue microenvironment: stress-induced cell-matrix adhesion and gap junction mediated cell-cell communication, respectively. Increase in cell numbers of tumour-initiating cells, which are cultured in suspension as cell clusters, and adherent differentiated cells can be blocked to a similar extent by Carbenoxolone, as both cell populations form gap junctions, but the adherent differentiated cells are much more sensitive to Disulfiram treatment, which - via modulation of NF-κB signalling - interferes with cell-substrate adhesion.

sAPPβ and sAPPα increase structural complexity and E/I input ratio in primary hippocampal neurons and alter Ca homeostasis and CREB1-signaling.

One major pathophysiological hallmark of Alzheimer's disease (AD) is senile plaques composed of amyloid β (Aβ). In the amyloidogenic pathway, cleavage of the amyloid precursor protein (APP) is shifted towards Aβ production and soluble APPβ (sAPPβ) levels. Aβ is known to impair synaptic function; however, much less is known about the physiological functions of sAPPβ.

Targeting Spinal Long-Term Potentiation as a Basis for Analgesia Recent Developments.

Recent investigations of pain mechanisms leading to the induction and maintenance of long-term potentiation (LTP) in the spinal cord have identified a huge number of molecular targets that might be appropriate for therapeutically intervention. In this short review we summarize recently published studies investigating drugs that affect LTP in the spinal cord. After providing an overview of spinal pain pathways and of the respective methods for their investigation, molecular targets for possible pharmacological interventions are discussed.

Targeting spinal long-term potentiation as a basis for anlagesia: recent developments.

Recent investigations of pain mechanisms leading to the induction and maintenance of long-term potentiation (LTP) in the spinal cord have identified a huge number of molecular targets that might be appropriate for therapeutically intervention. In this short review we summarize recently published studies investigating drugs that affect LTP in the spinal cord. After providing an overview of spinal pain pathways and of the respective methods for their investigation, molecular targets for possible pharmacological interventions are discussed.

Intranasal application of xenon reduces opioid requirement and postoperative pain in patients undergoing major abdominal surgery: a randomized controlled trial.

Background: Both central sensitization after peripheral tissue injury and the development of opioid tolerance involve activation of N-methyl-D-aspartate (NMDA) receptors. At subanesthetic doses the NMDA receptor antagonist xenon suppresses pain-evoked sensitization of pain-processing areas in the central nervous system. Although numerous studies describe the effect of NMDA receptor antagonists on postoperative pain, clinical studies elucidating their intraoperative analgesic potency when applied in a low dosage are still largely missing.

Molecular and physiological evidence for functional gamma-aminobutyric acid (GABA)-C receptors in growth hormone-secreting cells.

The neurotransmitter gamma-aminobutyric acid (GABA), released by hypothalamic neurons as well as by growth hormone- (GH) and adrenocorticotropin-producing cells, is a regulator of pituitary endocrine functions. Different classes of GABA receptors may be involved. In this study, we report that GH cells, isolated by laser microdissection from rat pituitary slices, possess the GABA-C receptor subunit rho2.