Search results for "Calcium Channel"
showing 10 items of 204 documents
Separation of presynaptic Cav2 and Cav1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca2+ pump PMCA
2021
Significance Synaptic vesicle (SV) release from presynaptic terminals requires nanometer precise control of action potential (AP)–triggered calcium influx through voltage-gated calcium channels (VGCCs). SV recycling also depends on calcium signals, though in different spatiotemporal domains. Mechanisms for separate control of SV release and recycling by AP-triggered calcium influx remain elusive. Here, we demonstrate largely independent regulation of release and recycling by two different populations of VGCCs (Cav2, Cav1), identify Cav1 as one of potentially multiple calcium entry routes for endocytosis regulation, and show functional separation of simultaneous calcium signals in the nanome…
Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Nifedipine
2015
Literature data relevant to the biopharmaceutical properties of the active pharmaceutical ingredient (API) nifedipine are reviewed to evaluate whether a waiver of in vivo bioequivalence (BE) testing of immediate-release (IR) dosage forms formulated as tablets and soft gelatin capsules is warranted. Nifedipine's solubility and permeability, its therapeutic use and index, pharmacokinetics, food drug interactions, and any reported BE/bioavailability problems were all taken into consideration. Solubility and BA data indicate conclusively that nifedipine is a class II substance of biopharmaceutics classification system (BCS) and that the formulation of drug product plays a key role on the dissol…
Oxysterol mixture in hypercholesterolemia-relevant proportion causes oxidative stress-dependent eryptosis.
2014
Background/Aims: Oxysterol activity on the erythrocyte (RBC) programmed cell death (eryptosis) had not been studied yet. Effects of an oxysterol mixture in hyper-cholesterolemic-relevant proportion, and of individual compounds, were investigated on RBCs from healthy humans. Methods: Membrane phosphatidylserine (PS) externalization, calcium entry, ROS production, amino-phospholipid translocase (APLT) activity were evaluated by cytofluorimetric assays, cell volume from forward scatter. Prostaglandin PGE2 was measured by ELISA; GSH-adducts and lipoperoxides by spectrophotometry. Involvement of protein kinase C and caspase was investigated by inhibitors staurosporin, calphostin C, and Z-DEVD-FM…
Design of pharmacophoric group containing 1,4-dihydropyridine derivatives and determination of spectrum of pharmacological activities
2017
Vairākkārtīgi ir uzsvērts, ka 1,4-dihidropiridīna cikls ir viens no farmakoloģiski priviliģētām struktūrām, kas iedarbojas uz jonu kanāliem un dažādiem receptoriem, un kuru modificējot, sintezējot tās struktūras analogus, variējot aizvietotājus molekulā, būtu iespējams iegūt dažādus farmakoloģiski aktīvus savienojumus. Pētījumā ir sintezēti jauni, mērķtiecīgi dizainēti, farmakoforas grupas saturoši 1,4-dihidropiridīna atvasinājumi, sistemātiski mainot farmakoforās grupas (piridīniju un/vai propargil) un to atrašanās vietu molekulā. Izvērtēts sintezēto savienojumu farmakoloģiskās darbības spektrs (aktivitāte uz kalcija kanāliem, antiradikālā aktivitāte un reducējošā kapacitāte), veidots stru…
Differential gene expression analysis identifies murine Cacnb3 as strongly upregulated in distinct dendritic cell populations upon stimulation
2011
Langerhans cells (LCs) represent the dendritic cell (DC) population in the epidermis. Among the set of genes induced in primary mouse LCs in response to stimulation, both isoforms of the voltage-dependent Ca²(+) channel (VDCC) regulatory subunit Cacnb3 as well as the DC maturation marker Fscn1 were upregulated most strongly. Comparable results were obtained for a recently described myeloid DC line (SP37A3). Other antigen presenting cell populations, namely, bone marrow-derived DCs, macrophages and primary B cells, showed no stimulation-associated upregulation of Cacnb3 expression. Pharmacological inhibition of Ca²(+) channel activity during the stimulation of SP37A3 cells enhanced their T c…
COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis.
2022
Background: iron and calcium dysmetabolism, with hyperferritinemia, hypoferremia, hypocalcemia and anemia have been documented in the majority of COVID-19 patients at later/worse stages. Furthermore, complementary to ACE2, both sialic acid (SA) molecules and CD147 proved relevant host receptors for SARS-CoV-2 entry, which explains the viral attack to multiple types of cells, including erythrocytes, endothelium and neural tissue. Several authors advocated that cell ferroptosis may be the core and final cell degenerative mechanism. Methods: a literature research was performed in several scientific search engines, such as PubMed Central, Cochrane Library, Chemical Abstract Service. More than 5…
Association of Whirlin with Cav1.3 (α1D) Channels in Photoreceptors, Defining a Novel Member of the Usher Protein Network
2010
Contains fulltext : 88383.pdf (Publisher’s version ) (Closed access) PURPOSE: Usher syndrome is the most common form of hereditary deaf-blindness. It is both clinically and genetically heterogeneous. The USH2D protein whirlin interacts via its PDZ domains with other Usher-associated proteins containing a C-terminal type I PDZ-binding motif. These proteins co-localize with whirlin at the region of the connecting cilium and at the synapse of photoreceptor cells. This study was undertaken to identify novel, Usher syndrome-associated, interacting partners of whirlin and thereby obtain more insights into the function of whirlin. METHODS: The database of ciliary proteins was searched for proteins…
Cytosolic Ca2+ and Phosphoinositide Hydrolysis Linked to Constitutively Active α1d-Adrenoceptors in Vascular Smooth Muscle
2003
In the present study, we analyzed changes in intracellular Ca2+ levels and inositol phosphate accumulation related to a population of alpha 1d-adrenoceptors in rat aorta resembling constitutively active receptors. Following intracellular Ca2+ store depletion by noradrenaline in Ca2+-free medium and removal of the agonist, restoration of extracellular Ca2+ induced four signals: a biphasic (transient and sustained) increase in [Ca2+]i, inositol phosphate accumulation, and a contractile response in the aorta. The transient increase in Ca2+, the inositol phosphate accumulation, and the contractile response were not observed in aortae incubated with prazosin or BMY 7378 [8-[2-[4-(2-methoxyphenyl…
Possible Ca 2+ -dependent mechanism of apical outer hair cell modulation within the cochlea of the guinea pig
1998
Calcium ions were precipitated with potassium antimonate after injection of the inorganic calcium channel blocker MnCl2 or the inorganic potassium channel blockers BaCl2 or CsCl into the perilymph of the scala vestibuli of the guinea pig. The spatial distribution of the formed histochemical reaction products within the organ of Corti was studied by energy-filtering transmission-electron microscopy. Compared with untreated control ears, the number of the formed precipitates drastically increased at the extracellular side of the lamina reticularis after application of the various inorganic channel blockers. The apical side of the outer hair cells and the intervening Deiter cells were covered …
Effects of Anandamide and Noxious Heat on Intracellular Calcium Concentration in Nociceptive DRG Neurons of Rats
2007
As an endogenous agonist at the cannabinoid receptor CB1 and the capsaicin-receptor TRPV1, anandamide may exert both anti- and pronociceptive actions. Therefore we studied the effects of anandamide and other activators of both receptors on changes in free cytosolic calcium ([Ca2+]i) in acutely dissociated small dorsal root ganglion neurons (diameter: ≤30 μm). Anandamide (10 μM) increased [Ca2+]iin 76% of the neurons. The EC50was 7.41 μM, the Hill slope was 2.15 ± 0.43 (mean ± SE). This increase was blocked by the competitive TRPV1-antagonist capsazepine (10 μM) and in Ca2+-free extracellular solution. Neither exclusion of voltage-gated sodium channels nor additional blockade of voltage-gate…