Search results for "Ouabain"
showing 10 items of 37 documents
α2 isoform of Na+,K+-ATPase via Na+,Ca2+ exchanger modulates myelin basic protein synthesis in oligodendrocyte lineage cells in vitro
2018
Abstract Oligodendrocytes in the CNS myelinate neuronal axons, facilitating rapid propagation of action potentials. Myelin basic protein (MBP) is an essential component of myelin and its absence results in severe hypomyelination. In oligodendrocyte lineage cell (OLC) monocultures MBP synthesis starts at DIV4. Ouabain (10 nM), a Na+,K+-ATPase (NKA) blocker, stimulates MBP synthesis. As OLCs express the α2 isoform of NKA (α2-NKA) that has a high affinity for ouabain, we hypothesized that α2-NKA mediates this effect. Knockdown of α2-NKA with small interfering (si)RNA (α2-siRNA) significantly potentiated MBP synthesis at DIV4 and 5. This effect was completely blocked by KB-R7943 (1 μM), a Na+,C…
Intracellular ion signaling influences myelin basic protein synthesis in oligodendrocyte precursor cells
2016
Myelination in the central nervous system depends on axon-oligodendrocyte precursor cell (OPC) interaction. We suggest that myelin synthesis may be influenced by [Na+]i and [Ca2+]i signaling in OPCs. Experiments were performed in mouse cultured OPCs at day in vitro (DIV) 2-6 or acute slices of the corpus callosum at postnatal days (P) 10-30. Synthesis of Myelin Basic Protein (MBP), an "executive molecule of myelin", was used as readout of myelination. Immunohistological data revealed that MBP synthesis in cultured OPCs starts around DIV4. Transient elevations of resting [Ca2+]i and [Na+]i levels were observed in the same temporal window (DIV4-5). At DIV4, but not at DIV2, both extracellular…
Ryanodine receptor- and sodium-calcium exchanger-mediated spontaneous calcium activity in immature oligodendrocytes in cultures
2019
Myelination in the central nervous system depends on interactions between axons and oligodendrocyte precursor cells (OPCs). Action potentials in an axon can be followed by release of biologically active substances, like glutamate, which can instruct OPCs to start myelination. Myelin Basic Protein (MBP) is an "executive molecule of myelin" required for the formation of compact myelin. As cells of the oligodendrocyte lineage (OLCs) are capable of producing MBP in pure oligodendrocyte cultures, i.e. without neurons, we investigated Ca2+ signaling in developing OLCs in cultures. We show that spontaneous Ca2+ transients (CTs) occur at very low frequency in both bipolar OPCs and mature oligodendr…
Effect of ouabain and furosemide on erythrocyte sodium and phosphate transport.
1981
The effects of ouabain and furosemide on the unidirectional efflux of sodium and phosphate ions were studied in freshly drawn human red blood cells (RBCs). In the presence of physiologic concentrations of sodium and potassium the rate of sodium efflux was reduced by 74% due to ouabain sensitivity. Furosemide (1.0 mmol/l) reduced ouabain-insensitive sodium transport rate by a further 50%. Thus, 13% of total sodium efflux was inhibited by furosemide when ouabain was present. In the absence of ouabain, however, furosemide inhibited 31% of total sodium transport, indicating that it also affected ouabain-sensitive sodium efflux. Phosphate transfer of RBCs was almost 1.0 mmol/l RBCs per hour. Ery…
Role of Ca2+-activated K+ channels and Na+,K+-ATPase in prostaglandin E1- and E2-induced inhibition of the adrenergic response in human vas deferens
2011
We studied the role of K(+) channels and Na(+),K(+)-ATPase in the presynaptic inhibitory effects of prostaglandin E(1) (PGE(1)) and PGE(2) on the adrenergic responses of human vas deferens. Furthermore, we determined the effects of increasing extracellular K(+) concentrations ([K(+)](o)) and inhibition of Na(+),K(+)-ATPase on neurogenic and norepinephrine-induced contractile responses. Ring segments of the epididymal part of the vas deferens were taken from 45 elective vasectomies and mounted in organ baths for isometric recording of tension. The neuromodulatory effects of PGEs were tested in the presence of K(+) channel blockers. PGE(1) and PGE(2) (10(-8) to 10(-6)M) induced inhibition of …
Endothelium-dependent responses in human isolated thyroid arteries from donors
2004
The functional properties of the endothelium of human thyroid arteries remain unexplored. We investigated the intervention of nitric oxide (NO), prostacyclin (PGI(2)) and endothelium-derived hyperpolarizing factor (EDHF) in the responses to acetylcholine and noradrenaline in isolated thyroid arteries obtained from multi-organ donors. Artery rings were suspended in organ baths for isometric recording of tension. The contribution of NO, PGI(2) and EDHF to endothelium-dependent relaxation was determined by the inhibitory effects of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin, and K(+) channel inhibitors respectively. Acetylcholine induced concentration-dependent relaxation; this effect w…
OASIS-HT: design of a pharmacogenomic dose-finding study.
2005
Experimental evidence and observations in humans strongly support an interactive role of mutated α-adducin, sodium (Na+)/potassium (K+)-adenosine triphosphatase (ATPase) activity and endogenous ouabain in Na+homeostasis and the pathogenesis of hypertension. The Ouabain and Adducin for Specific Intervention on Sodium in HyperTension (OASIS-HT) trial is an early Phase II dose-finding study, which will be conducted across 39 European centers. Following a run-in period of 4 weeks without treatment, eligible patients will be randomized to one of five oral doses of rostafuroxin consisting of 0.05, 0.15, 0.5, 1.5, or 5.0 mg/day. Each dose will be compared to a placebo in a double-blind crossover e…
Coordinate mutation and transformation of mouse fibroblasts: induction by nitroquinoline oxide and modulation by caffeine
1981
Mutation and malignant transformation were followed in the same cells. Mouse fibroblasts (C3H 10T 1/2) were mutated and transformed by 4-nitroquinoline-1-oxide with similar, approximately linear dose-responses. The presence of caffeine immediately after exposure to 4-nitroquinoline-1-oxide potently inhibited mutation and transformation at high but not at low doses of 4-nitroquinoline-1-oxide. Whilst the coordinate induction of mutation and transformation could be explained by both a common target (DNA) or a common reactive species hitting several targets, the identical modulation by a DNA repair inhibitor of both end points suggests fundamental similarities in the nature of the lesions lead…
Ouabain enhances release of acetylcholine in the heart evoked by unilateral vagal stimulation.
1986
The aim of the study was to elucidate peripheral effects of ouabain on the parasympathetic innervation of the heart, effects that could contribute to the experimentally and clinically well established “vagal effect of cardiac glycosides”. The experiments were carried out with ouabain concentrations of 3×10−7 and 10−6 mol/l, which were considered “therapeutic”, as they increased force of contraction and did not elicit arrhythmias in incubated chicken atria. In atrial preparations of chickens and guinea-pigs the negative chronotropic and inotropic effects of acetylcholine (ACh) were not altered by 3×10−7 mol/l ouabain. Resting efflux of ACh from perfused chicken hearts was increased by ouabai…
Effects of phorbol 12,13-diacetate on human isolated bronchus
2000
Protein kinase C appears to be involved in the regulation of airway contractility. Phorbol 12,13-diacetate (PDA; 0.01-10 microM), a protein kinase C activator, produced a transient relaxation followed by a sustained contraction of human isolated bronchus. Different protein kinase C inhibitors (calphostin C, staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine) (H-7), nifedipine (NIF; 1 microM) or incubation with Ca(2+)-free medium, inhibited the spasmogenic response to phorbol, while ouabain (10 microM) suppressed only the initial relaxation. These results indicate that the initial relaxation, in response to PDA, is related to the activation of Na(+)/K(+)-ATPase, while the ensuin…