Search results for "M2"
showing 10 items of 256 documents
Murine embryonic stem cell line CGR8 expresses all subtypes of muscarinic receptors and multiple nicotinic receptor subunits: Down-regulation of α4- …
2015
Non-neuronal acetylcholine mediates its cellular effects via stimulation of the G-protein-coupled muscarinic receptors and the ligand-gated ion channel nicotinic receptors. The murine embryonic stem cell line CGR8 synthesizes and releases non-neuronal acetylcholine. In the present study a systematic investigation of the expression of nicotinic receptor subunits and muscarinic receptors was performed, when the stem cells were grown in the presence or absence of LIF, as the latter condition induces early differentiation. CGR8 cells expressed multiple nicotinic receptor subtypes (α3, α4, α7, α9, α10, β1, β2, β3, β4, γ, δ, e) and muscarinic receptors (M1, M3, M4, M5); M2 was detected only in 2 …
Acetylcholine release at motor endplates and autonomic neuroeffector junctions: a comparison.
1996
Acetylcholine released at motor endplates and at autonomic neuroeffector junctions binds to nicotinic and muscarinic receptors to affect the activity of the corresponding target cells. Additionally, nicotonic and muscarinic receptors modulate various intracellular regulatory pathways (second messengers, gene expression) and mediate trophic effects. To maintain homeostasis of the individual cell and of the whole organism the release of acetylcholine has to be strictly controlled within both nervous systems. The basic events of synthesis, storage, and release are comparable at motoneurones and autonomic neurones, but mechanisms regulating transmitter release appear to differ. The motor endpla…
Non-neuronal acetylcholine, a locally acting molecule, widely distributed in biological systems: expression and function in humans.
1998
Acetylcholine acts as a neurotransmitter in the central and peripheral nervous systems in humans. However, recent experiments demonstrate a widespread expression of the cholinergic system in non-neuronal cells in humans. The synthesizing enzyme choline acetyltransferase, the signalling molecule acetylcholine, and the respective receptors (nicotinic or muscarinic) are expressed in epithelial cells (human airways, alimentary tract, epidermis). Acetylcholine is also found in mesothelial, endothelial, glial, and circulating blood cells (platelets, mononuclear cells), as well as in alveolar macrophages. The existence of non-neuronal acetylcholine explains the widespread expression of muscarinic …
Pho85 and PI(4,5)P(2) regulate different lipid metabolic pathways in response to cold
2019
Lipid homeostasis allows cells to adjust membrane biophysical properties in response to changes in environmental conditions. In the yeast Saccharomyces cerevisiae, a downward shift in temperature from an optimal reduces membrane fluidity, which triggers a lipid remodeling of the plasma membrane. How changes in membrane fluidity are perceived, and how the abundance and composition of different lipid classes is properly balanced, remain largely unknown. Here, we show that the levels of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], the most abundant plasma membrane phosphoinositide, drop rapidly in response to a downward shift in temperature. This change triggers a signaling cascade trans…
Search for multiwavelength emission from the binary millisecond pulsar PSR J1836-2354A in the globular cluster M22
2019
We present a multi-band search for X-ray, optical and $\gamma$-ray emission of the radio binary millisecond pulsar J1836-2354A, hosted in the globular cluster M22. X-ray emission is significantly detected in two Chandra observations, performed in 2005 and 2014, at a luminosity of $\sim$2-3$\times$10$^{30}$ erg s$^{-1}$, in the 0.5-8 keV energy range. The radio and the X-ray source positions are found consistent within 1$\sigma$ error box. No detection is found in archival XMM-Newton and Swift/XRT observations, compatible with the Chandra flux level. The low statistics prevents us to assess if the X-ray source varied between the two observations. The X-ray spectrum is consistent with a power…
Mortality risk attributable to wildfire-related PM2·5 pollution: a global time series study in 749 locations
2021
Summary Background Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world. Methods For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000–16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem …
Molecular Alterations of the RBI, TP53, and MDM2 Genes in Primary and Xenografted Human Osteosarcomas
1997
We report the status of the RBI, TP53, and MDM2 genes in human osteosarcomas and cell lines established from surgical specimens and transplanted into athymic naked mice. By using reverse transcriptase-polymerase chain reaction (RT-PCR) as a prescreening technique and posterior sequencing, we observe
Molecular dynamics studies on Mdm2 complexes: An analysis of the inhibitor influence
2012
p53 is a powerful anti-tumoral molecule frequently inactivated by mutations or deletions in cancer. However, half of all human tumors expresses wild-type p53, and its activation, by antagonizing its negative regulator Mdm2, might offer a new strategy for therapeutic protocol. In this work, we present a molecular dynamics study on Mdm2 structure bound to two different known inhibitors with the aim to investigate the structural transitions between apo-Mdm2 and Mdm2-inhibitor complexes. We tried to gain information about conformational changes binding a benzodiazepine derivative inhibitor with respect the known nutlin and the apo form. The conformational changes alter the size of the cleft and…
Muscarinic M2 receptors in acetylcholine-isoproterenol functional antagonism in human isolated bronchus
2002
The muscarinic functional antagonism of isoproterenol relaxation and the contribution of muscarinic M2 receptors were examined in human isolated bronchus. In intact tissues, acetylcholine (ACh) precontraction decreased isoproterenol potency and maximal relaxation (−log EC50 shift = −1.49 ± 0.16 and Emax inhibition for 100 μM ACh = 30%) more than the same levels of histamine contraction. The M2receptor-selective antagonist methoctramine (1 μM) reduced this antagonism in ACh- but not histamine-contracted tissues. Similar results were obtained for forskolin-induced relaxation. After selective inactivation of M3 receptors with 4-diphenylacetoxy- N-(2-chloroethyl)piperadine hydrochloric acid (3…
Finite type invariants of knots in homology 3-spheres with respect to null LP-surgeries
2017
We study a theory of finite type invariants for null-homologous knots in rational homology 3-spheres with respect to null Lagrangian-preserving surgeries. It is an analogue in the setting of the rational homology of the Goussarov-Rozansky theory for knots in integral homology 3-spheres. We give a partial combinatorial description of the graded space associated with our theory and determine some cases when this description is complete. For null-homologous knots in rational homology 3-spheres with a trivial Alexander polynomial, we show that the Kricker lift of the Kontsevich integral and the Lescop equivariant invariant built from integrals in configuration spaces are universal finite type i…