Search results for "Calcium Signaling"
showing 10 items of 96 documents
The cognition‐enhancing activity of E1R , a novel positive allosteric modulator of sigma‐1 receptors
2013
Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test…
Effects of Presynaptic Mutations on a Postsynaptic Cacna1s Calcium Channel Colocalized with mGluR6 at Mouse Photoreceptor Ribbon Synapses
2008
Purpose Photoreceptor ribbon synapses translate light-dependent changes of membrane potential into graded transmitter release via L-type voltage-dependent calcium channel (VDCC) activity. Functional abnormalities (e.g., a reduced electroretinogram b-wave), arising from mutations of presynaptic proteins, such as Bassoon and the VDCCalpha1 subunit Cacna1f, have been shown to altered transmitter release. L-type VDCCalpha1 subtype expression in wild-type and mutant mice was examined, to investigate the underlying pathologic mechanism. Methods Two antisera against Cacna1f, and a Cacna1f mouse mutant (Cacna1fDeltaEx14-17) were generated. Immunocytochemistry for L-type VDCCalpha1 subunits and addi…
A Multiomics Study To Unravel the Effects of Developmental Exposure to Endosulfan in Rats: Molecular Explanation for Sex-Dependent Effects
2019
Exposure to low levels of environmental contaminants, including pesticides, induces neurodevelopmental toxicity. Environmental and food contaminants can reach the brain of the fetus, affecting brain development and leading to neurological dysfunction. The pesticide endosulfan is a persistent pollutant, and significant levels still remain detectable in the environment although its use is banned in some countries. In rats, endosulfan exposure during brain development alters motor activity, coordination, learning, and memory, even several months after uptake, and does so in a sex-dependent way. However, the molecular mechanisms driving these effects have not been studied in detail. In this wor…
Acetylsalicylic acid reduces heat responses in rat nociceptive primary sensory neurons – evidence for a new mechanism of action
2002
Acetylsalicylic acid (ASA) is thought to exert its peripheral analgesic effects via inhibition of cyclooxygenase. We now studied the effects of ASA on heat responses in primary nociceptive neurons by whole-cell patch-clamp and calcium microfluorimetry experiments. Heat-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons were significantly reduced by ASA in a dose-dependent and reversible manner (IC(50) 375 nM, Hill slope -2.2, maximum effect 55%). Heat-evoked calcium transients (measured with FURA-2) were reversibly reduced by 53+/-14% (P0.05) by co-application of 1 microM ASA. The low IC(50) value, the rapid occurrence, and the reversibility of the observed effec…
Changes in cytosolic calcium in response to noxious heat and their relationship to vanilloid receptors in rat dorsal root ganglion neurons.
2001
Heat transduction mechanisms in primary nociceptive afferents have been suggested to involve a vanilloid receptor channel with high calcium permeability. To characterize the changes in free cytosolic calcium evoked by noxious heat stimuli (< or =51 degrees C, 10s), we performed microfluorometric measurements in acutely dissociated small dorsal root ganglion neurons (< or =32.5 microm) of adult rats using the dye FURA-2. Only neurons that responded with a reversible increase in intracellular calcium to high potassium were evaluated. Heat-induced calcium transients (exceeding mean + 3S.D. of the temperature dependence of the dye) were found in 66 of 105 neurons. These transients increased non…
Identification of Patulin from
2019
The identification and characterization of fungal commensals of the human gut (the mycobiota) is ongoing, and the effects of their various secondary metabolites on the health and disease of the host is a matter of current research. While the neurons of the central nervous system might be affected indirectly by compounds from gut microorganisms, the largest peripheral neuronal network (the enteric nervous system) is located within the gut and is exposed directly to such metabolites. We analyzed 320 fungal extracts and their effect on the viability of a human neuronal cell line (SH-SY5Y), as well as their effects on the viability and functionality of the most effective compound on primary ent…
Activation of P2Y receptors by ATP and by its analogue, ADPbetaS, triggers two calcium signal pathways in the longitudinal muscle of mouse distal col…
2008
Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanisms leading to the intracellular calcium concentration increase necessary to trigger muscular contraction. Motor responses of mouse colonic longitudinal muscle to P2Y receptor agonists were examined in vitro as changes in isometric tension. ATP or ADPbetaS induced muscular contraction, which was not affected by P2Y(11) or P2Y(13) selective antagonists. Calcium-free solution or th…
Induction of RAGE Shedding by Activation of G Protein-Coupled Receptors
2011
The multiligand Receptor for Advanced Glycation End products (RAGE) is involved in various pathophysiological processes, including diabetic inflammatory conditions and Alzheimers disease. Full-length RAGE, a cell surface-located type I membrane protein, can proteolytically be converted by metalloproteinases ADAM10 and MMP9 into a soluble RAGE form. Moreover, administration of recombinant soluble RAGE suppresses activation of cell surface-located RAGE by trapping RAGE ligands. Therefore stimulation of RAGE shedding might have a therapeutic value regarding inflammatory diseases. We aimed to investigate whether RAGE shedding is inducible via ligand-induced activation of G protein-coupled recep…
In vitro tracheal hyperresponsiveness to muscarinic receptor stimulation by carbachol in a rat model of bleomycin-induced pulmonary fibrosis
2006
Summary 1 Bleomycin-induced lung injury is widely used as an experimental model to investigate the pathophysiology of pulmonary fibrosis but the alterations in the pharmacological responsiveness of airways isolated from bleomycin-exposed animals has been scarcely investigated. The aim of this study was to examine the in vitro tracheal responses to muscarinic receptor stimulation with carbachol in a rat bleomycin model. 2 Concentration–response curves to carbachol (10 nm to 0.1 mm) were obtained in tracheal rings isolated from Sprague–Dawley rats 14 days after endotracheal bleomycin or saline. The intracellular calcium signal in response to carbachol (10 μm) was measured by epifluorescence m…
Dietary (n-3) polyunsaturated fatty acids exert antihypertensive effects by modulating calcium signaling in T cells of rats.
2001
After 10 wk of feeding an experimental diet enriched with (n-3) polyunsaturated fatty acids (PUFA), i.e., eicosapentaenoic acid [EPA, 20:5(n-3)] and [DHA, 22:6(n-3)] (EPAX), blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats was reduced relative to rats fed an unsupplemented control diet. Concanavalin A-stimulated T-cell proliferation was diminished in both strains of rats fed the PUFA/EPAX diet. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. To determine whether there was a defect in calcium homeostasis in T cells during hypertension, we employed the followin…