40 results about "Intracellular ca" patented technology

An intracellular calcium concentration increase inhibitor containing as the active ingredient (1) a boron compound represented by the formula (I).

The compound represented by the formula (I) inhibits the increase of the intracellular calcium concentration, and therefore it is deemed to be useful as an agent for the prophylaxis and/or treatment of platelet aggregation, ischemic diseases in hearts and brains, immune deficiency diseases, allorgosis, bronchial asthma, hypertension, cerebrovascular spasm, various renal diseases, pancreatitis, Alzheimer's disease, etc.

An exemplary method of screening compositions for insect control activity includes, providing an insect cell expressing a receptor of the insect olfactory cascade or fragment thereof, contacting a test composition to the insect cell, measuring at least one parameter selected from olfactory cascade receptor binding affinity, intracellular cAMP levels, and intracellular Ca²⁺ levels, and selecting a compound capable of altering at least one of parameter selected from increased olfactory cascade receptor binding affinity, altered intracellular cAMP levels, and altered intracellular Ca²⁺ levels. An exemplary isolated eukaryotic cell is transformed with a nucleic acid encoding an insect olfactory cascade receptor protein or fragment thereof. An exemplary method for controlling an insect includes, contacting a composition including a compound having a binding affinity for an olfactory cascade receptor of an insect.

Described herein are methods for controlling the intracellular calcium concentration in a subject prior to experiencing an ischemic event, while experiencing an ischemic event, or while suffering from ischemia. The methods comprise administering an effective amount of O-desulfated heparin to the subject. The methods described herein are also useful in treating the symptoms associated with ischemic events or ischemia.

A method for decreasing blood glucose levels is disclosed. Iptakalim hydrochloride (a SUR1 subunit-dependent K_ATP channel blocker and a SUR2 subunit-selective K_ATP channel opener) is used to block pancreatic β-cell K_ATP channels, which depolarizes β-cells, elevates intracellular Ca²⁺ concentrations, and in turn increases insulin release. Therefore, in some implementations, iptakalim hydrochloride is an optimal treatment for type-2 diabetic patients with cardiovascular disorders.

The present invention relates to the use of a compound of formula (1):

wherein: R1 comprises a carbonyl group and R2 is a hydrocarbyl group; optionally wherein said ring is further substituted; or a pharmaceutically acceptable salt thereof; in the manufacture of a medicament for use in one or more of: modulating the release of intracellular calcium from a store controlled by nicotinic acid adenine dinucleotide phosphate; modulating calcium spikes in mammalian cells; treating diseases in one or more of brain, heart, pancreatic cells (e.g. pancreatic acinar and pancreatic beta cells), immune cells, T-cells, haemopoietic cells including phagocytes; treating diseases in one or more of brain, heart, pancreatic cells (e.g. pancreatic acinar and pancreatic beta cells), immune cells, T-cells, haemopoietic cells including phagocytes by modulating the release of intracellular calcium from a store controlled by nicotinic acid adenine dinucleotide phosphate; treating diseases in one or more of brain, heart, and T-cells by modulating calcium spikes in mammalian cells.

The invention discloses a 1,3,4-oxadiazole derivative and a synthetic method thereof, and an application of the derivative serving as a fluorescent indicator to detection of intracellular calcium ions (Ca<2+>). The method comprises the following steps of: under the protection of inert gas, performing a wittig reaction on the 1,3,4-oxadiazole derivative and a calcium ion response group to obtain a crude product; and concentrating the crude product, and separating through a silica gel column to obtain a pure product. The 1,3,4-oxadiazole derivative has the advantages of high sensitivity and high selectivity on Ca<2+>, large Stocks displacement, proportional measurement and the like; the color of the indicator changes greatly before and after bonding with Ca<2+>, so that identification and judgment can be performed conveniently through naked eyes; and moreover, the indicator can be loaded into cells, so that an intracellular Ca<2+> signal and the concentration thereof can be detected conveniently under a laser confocal microscope.

Stem or progenitor cells, including cells derived from bone marrow, exhibit increased intracellular Ca²⁺ mobilization and alterations in gene expression and proliferation when subjected to an oscillatory fluid flow.

Analysis of substance capable of binding with inositol-1,4,5-triphosphate (IP₃) receptor (IP₃R), preferably with a regulation domain of IP₃R; analysis of the function of IP₃R; and establishing of a method of treatment or diagnosis for various malfunctions and diseases associated with IP₃R. In particular, control of the activity of intracellular Ca²⁺ release. More specifically, a regulator for the activity of inositol-1,4,5-triphosphate (IP₃) receptor (IP₃R), comprised of carbonic anhydrase related protein (CARP); a control agent for intracellular calsium release, comprised of carbonic anhydrase related protein (CARP); and a method of control therewith.

The invention provides an application of a calcium ion carrier and derivatives thereof in preparation of a medicine for treating leucoderma, and aims to solve the problem that melanocytes at an affected part of leucoderma have obstacles in uptake and transport of calcium ions. The calcium ion carrier is smeared on the affected part to increase the intake of calcium ions by melanocytes at the affected part so that the calcium steady state of the melanocytes is improved and recovered, a better intracellular calcium environment is provided for leucoderma treatment, the synthesis and transportation of melanin are promoted, and the defense of the melanocytes to free radicals and oxidative stress is enhanced. The application aims to serve as an adjuvant drug of the existing leucoderma treatmentdrug and method, and the existing treatment drug and method are assisted by improving the calcium environment in melanocytes of the affected part of leucoderma so that the treatment effect of the existing drug and method is improved, the treatment result is consolidated, and the disease recurrence rate is reduced.

The invention discloses application of virus macrophage inflammatory protein vMIP-II for inducing dephosphorylation of CD8<+> T cells to form Tcm. The vMIP-II for inducing dephosphorylation of the CD8<+> T cells to form the Tcm is developed in a laboratory and is verified by the National Institute for Control of Pharmaceutical and Biological Products. According to the invention, the CD8<+> T cellsare researched through a rhesus SIV infection model. The research finds that: the vMIP-II can enable Tcm to be proliferated depending on the dosage of the vMIP-II, and the differential gene of the proliferative cell is mainly enriched in a chemokine receptor and a phosphorylation pathway. The research further finds that: the proliferation is as follows: the vMIP-II closes a CD8<+> T chemokine receptor, promotes low expression of G protein, reduces the concentration of intracellular Ca<2+> and mitochondrial membrane potential, inhibits phosphorylation related genes, and promotes low expressionof phosphorylated proteins ERK1/2 and Akt, so that a CD8<+> T phosphorylation signal is weakened, metabolic reprogramming is carried out, and the CD8<+> T is converted into the Tcm. Therefore, the discovery of the vMIP-II action mechanism provides a brand-new strategy for drug research and development of HIV/SIV infected AIDS, provides a new means for adoptive immunotherapy of virus resistance and tumor resistance, and has important clinical application value.

The present invention relates to a novel communication mechanism between astrocytes and neurons at a synapse. More specifically, the present invention relates to a signaling mechanism between astrocytes and neurons, by activating astrocytic G-protein coupled receptors, thereby activating glutamate receptors on a membrane of neighboring postsynaptic neurons, resulting in increasing the level of intracellular Ca²⁺ and inducing a depolarization inward current to control neurotransmission in neurons.

Molecular cloning and expression of a prostaglandin F2alpha receptor which is linked to the signal transduction pathways via guanine nucleotide binding regulatory (G) proteins and measured by, for example, cAMP, IP3 or intracellular calcium. By constructing cell lines that express a prostaglandin F2alpha receptor, the affinities and efficacies of agonist and antagonist drugs with the receptor can be assessed. A recombinant DNA construct includes a vector and a DNA fragment encoding a prostaglandin F2alpha receptor. A host cell is transformed with a recombinant DNA construct, so that the DNA fragment is expressed and a prostaglandin F2alpha receptor is produced. Suitable host systems include eukaryotic and prokaryotic cells, especially mamalian cells such as rat or human. Additionally, for diagnostic purposes, antibodies to a prostaglandin F2alpha receptor can be prepared by producing all or a portion of the receptor protein and injecting these into various types of mammals. Using the resulting antibodies, expression of an F2alpha receptor cDNA, i.e. receptor protein in tissue and cells can be measured.

This invention relates to a simple end point assay for detection of transient intracellular Ca²⁺ with broad applicability to many Ca²⁺channel proteins comprising, Generation of expression constructs for the fusion proteins having the Ca^2+/calmodulin dependent protein kinase II (CaMKII) phosphorylation sites of NR2A or NR2B subunits of N-methyl-D-aspartate receptor (NMDAR) or the voltage gated potassium channel of Drosophila (Eag) or any protein sequence which binds to the T-site of CaMKII similar to NR2B, conjugated to mitochondrial localizing signal sequence, or mutants of these sequences as described herein. Generation of mammalian expression constructs of α-CaMKll as a chimera with green fluorescent protein (GFP-α-CaMKII) or its mutants as described herein. Site-Directed mutagenesis, Transfection, Ca²⁺ stimulation, imaging and quantification of the number of cells with Ca²⁺-dependent signal, wherein, NMDA receptor activity assay, TRPVI receptor activity assay, GluR4 receptor activity assay are performed to detect the activity Of Ca²⁺ channel proteins.

The purpose of the present invention is to provide a method which is designed to form an intracellular recording electrode for a cell by a simple operation which is less invasive to the cell and does not need a magnetic force, and with which the short-term or long-term intracellular potential can be accurately measured. More specifically, provided is a method comprising: securing, to a manipulator or the like, a holder provided on a conductor having a conductive nano structure at a tip; making the tip nano structure part penetrate a cell membrane while adjusting the amount of pressure applied to the target cell, thereby forming an intracellular recording electrode independently secured above the cell; and measuring the intracellular potential. The conductive nano structure at the tip and the conductor main body do not have to be magnetic but may be stuck together by magnetic force or may be formed as one body. When the cell membrane potential of a target cell cultured in a typical culture vessel is recorded, by forming the conductor main body of a magnetic electrode (MagEle) and independently securing same using a ring-shaped magnet that is provided on the lower surface of the culture vessel and that secures a light projection path or a light observation path through the center thereof, measurement of the intracellular potential of the target cell and fluorescent observation of changes in intracellular potential due to a light stimulus or intracellular calcium dynamics can be performed simultaneously.

A method of treating an activated fibroblast associated disease or pre-disease condition in a mammal comprising, administering a pharmaceutical composition including a therapeutically effective amount of a first therapeutic, wherein the first therapeutic is one of an intracellular Ca²⁺ elevator, a YAP/TAZ inhibitor, both a intracellular Ca²⁺ elevator and a YAP/TAZ inhibitor, or pharmacologically acceptable salts, solvates, esters, amides, clathrates, stereoisomers, enantiomers, prodrugs or analogs thereof, or a combination thereof.

The present invention describes calcium sensitive and selective maxi-K potassium channel opener/activator compounds that function to open maxi-K channels under conditions of high intracellular calcium concentrations, and which do not significantly affect the opening of maxi-K channel proteins under conditions of low or physiologically normal intracellular calcium concentrations. Methods of assaying for and using such compounds are also provided. According to the invention, whole cell voltage patch-clamp studies newly demonstrated that the ability of opener compounds, e.g., fluoro-oxindoles and chloro-oxindoles, to open maxi-K channels was sensitive to the intracellular Ca²⁺ concentration ([Ca²⁺])_i, i.e., more channels opened at more negative potentials. Particular fluoro-oxindole and chloro-oxindole compounds produced significant increases in whole-cell maxi-K potassium channel-mediated outward currents only in cells having higher [Ca²⁺]_i, compared with effects in lower [Ca²⁺]_i. Such compounds provide Ca²⁺-sensitive and selective openers of maxi-K channels which show maximum effectiveness under conditions of increased [Ca²⁺]_i and, as such, provide treatments for diseases and disorders in which cells undergo, or are subject to, traumatic stress due to high internal calcium levels, such as stroke.

The present invention relates to the use of ZnT-1, originally described as a zinc transporter, in the regulation of L-type calcium channels (LTCC). In this study, the inventors have unexpectedly demonstrated that ZnT-1 physically interacts with LTCC, regulating its function. Most importantly, the inventors have shown that ZnT-1 can regulate intracellular Ca₂₊ influx, and thus, its intracellular concentration. This is the first demonstration of a natural blocker for LTCC, and it is a promising breakthrough as a potential agent to be used in the treatment and/or prevention of cardiovascular diseases and related indications.

PL37 (RAARISLGPRICKAFTE [SEQ ID NO: 2]) is an Antisense Homolgoy Box peptide composed of amino acids 37 to 53 of C5a-anaphylatoxin. Complementary peptides, ASGAPAPGPAGPLRPMF (Pep-A [SEQ ID NO: 1]) and ASTAPARAGLPRLPKFF (Pep-B [SEQ ID NO: 3]) were designed and characterized. Pep-A bound to PL37 and to C5a with very slow dissociation, whereas Pep-B failed to bind at all. C5a was inactivated by 7 nM or more of Pep-A and this concentration of Pep-A inhibited induction of intracellular Ca⁺⁺ influx in neutrophils. Patch clamp studies also showed the effectiveness of Pep-A in C5a-receptor-expressing neuroblastoma cells. Pep-A administration prevented rats from C5a-mediated rapid lethal shock. A-Pep-A (Pep-A acetylated with alanine at the amino-terminus) was more stable in vivo and showed stronger inhibition of inflammatory reactions in mice and rats. Chemical modification of Pep-A (e.g., acetylation, or single or multiple amino acid replacement, insertion, or deletion within the native Pep-A sequence) will yield effective inhibitors, and will often improve inhibitory function on C5a anaphylatoxin. In such modified constructs it will often be desired to conserve some or all 5 prolines found in Pep-A to preserve inhibitory function on C5a.

The invention discloses a method for increasing tropane alkaloid content in belladonna hairy roots by using a calcium signal inhibitor, which is characterized in that extracellular Ca < 2 + > concentration is reduced by using a Ca < 2 + > specific chelating agent, or a Ca < 2 + >/CaM signal pathway in the belladonna hairy roots is inhibited by using a cell membrane Ca < 2 + > channel inhibitor or an intracellular Ca < 2 + > receptor calmodulin inhibitor, so that the content of tropane alkaloid in the belladonna hairy roots is increased. Therefore, the expression of related genes PMT, TRI, CYP80F1, H6H and ArAT4 in the synthetic route of the tropane alkaloids is induced, and the synthesis and accumulation of the tropane alkaloids hyoscyamine, anisodamine or scopolamine are promoted.

Described is a stable recombinant stem cell able to express an apophotoprotein and produce a bioluminescent signal in the presence of a suitable chromophore as substrate in response to intracellular calcium concentration variation; non human transgenic mammal and cell derivatives thereof produced by said cells; methods for identifying agents modulating the differentiation of stem cells towards a specific cell lineage; methods for identifying a ligand able to stimulate a specific cell lineage target; methods for identifying an antagonist to ligand known to stimulate a specific cell lineage target; uses of stable recombinant stem cells for in vitro testing of toxicity and/teratology of a substance.

This disclosure relates to an angiogenesis-related pharmaceutical composition using connective tissue growth factor, more particularly to a pharmaceutical composition for promoting angiogenesis containing the connective tissue growth factor or a pharmaceutical composition for inhibiting angiogenesis containing at least one selected from the group consisting of polypeptide, antibody and a compound binding to connective tissue growth factor. The fragment of connective tissue growth factor protein, which was found out in the present invention, is a binding region to FPRL1, effectively induces FPRL1-specific ERK phosphorylation, activates FPRL1 to increase intracellular Ca²⁺ concentration, and finally, effectively induces angiogenesis, and thus, the fragment of connective tissue growth factor may be useful for a pharmaceutical composition for promoting angiogenesis, while polypeptide, antibody or a compound binding to the fragment of connective tissue growth factor protein may be useful for a pharmaceutical composition for inhibiting angiogenesis.