A technique for fast application of heated solutions of different composition to cultured neurones

Dittert, Ivan; Vlachová, Viktorie; Knotková, Helena; Vitásková, Zdenka; Vyklický, Ladislav; Kress, Michaela; Reeh, Peter W.

doi:10.1016/s0165-0270(98)00051-x

Cited by 72 publications

(44 citation statements)

References 11 publications

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“…Experiments were performed at room temperature and only one neuron was tested per Petri dish. A seven barrel system with common outlet was used for fast drug administration and heat stimulation of single neurons (Dittert et al, 1998). Capsaicin-activated inward currents (I caps ) were elicited by applying 0.3 M capsaicin (Sigma) for 10 s followed by a 2 min washout with control solution.…”

Section: Sns-cre Mice Sns-gp130mentioning

confidence: 99%

A Key Role for gp130 Expressed on Peripheral Sensory Nerves in Pathological Pain

et al. 2009

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Interleukin-6 (IL-6) is a key mediator of inflammation. Inhibitors of IL-6 or of its signal transducing receptor gp130 constitute a novel class of anti-inflammatory drugs, which raise great hopes for improved treatments of painful inflammatory diseases such as rheumatoid arthritis. IL-6 and gp130 may enhance pain not only indirectly through their proinflammatory actions but also through a direct action on nociceptors (i.e., on neurons activated by painful stimuli). We found indeed that the IL-6/gp130 ligand-receptor complex induced heat hypersensitivity both in vitro and in vivo. This process was mediated by activation of PKC-␦ via Gab1/2/PI 3 K and subsequent regulation of TRPV1, a member of the transient receptor potential (TRP) family of ion channels. To assess the relevance of this direct pain promoting effect of IL-6, we generated conditional knock-out mice, which lack gp130 specifically in nociceptors, and tested them in models of inflammatory and tumor-induced pain. These mice showed significantly reduced levels of inflammatory and tumor-induced pain but no changes in immune reactions or tumor growth. Our results uncover the significance of gp130 expressed in peripheral pain sensing neurons in the pathophysiology of major clinical pain disorders and suggest their use as novel pain relieving agents in inflammatory and tumor pain.

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Section: Sns-cre Mice Sns-gp130mentioning

confidence: 99%

A Key Role for gp130 Expressed on Peripheral Sensory Nerves in Pathological Pain

et al. 2009

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“…Capsaicin-activated inward currents (I Caps ) were evoked at Ϫ80 mV holding potential. A seven-barrel system with common outlet was used for fast application of increasing capsaicin concentrations of 10 nM to 10 M (Dittert et al, 1998). Capsaicin was purchased from Sigma-Aldrich.…”

Section: Patch-clamp Recording Of Capsaicin-activated Currents and Vomentioning

confidence: 99%

Inhibitor κB Kinase β Deficiency in Primary Nociceptive Neurons Increases TRP Channel Sensitivity

Bockhart¹,

Constantin²,

Häussler³

et al. 2009

J. Neurosci.

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Inhibitor B kinase (IKK) regulates the activity of the transcription factor nuclear factor-B that normally protects neurons against excitotoxicity. Constitutively active IKK is enriched at axon initial segments and nodes of Ranvier (NR). We used mice with a Cre-loxPmediated specific deletion of IKK␤ in sensory neurons of the dorsal root ganglion (SNS-IKK␤ Ϫ/Ϫ ) to evaluate whether IKK plays a role in sensory neuron excitability and nociception. We observed increased sensitivity to mechanical, cold, noxious heat and chemical stimulation in SNS-IKK␤ Ϫ/Ϫ mice, with normal proprioceptive and motor functions as revealed by gait analysis. This was associated with increased calcium influx and increased inward currents in small-and medium-sized primary sensory neurons of SNS-IKK␤ Ϫ/Ϫ mice during stimulation with capsaicin or Formalin, specific activators of transient receptor potentials TRPV1 and TRPA1 calcium channels, respectively. In vitro stimulation of saphenous nerve preparations of SNS-IKK␤ Ϫ/Ϫ mice showed increased neuronal excitability of A-and C-fibers but unchanged A-and C-fiber conduction velocities, normal voltage-gated sodium channel currents, and normal accumulation of ankyrin G and the sodium channels Nav1.6 at NR. The results suggest that IKK␤ functions as a negative modulator of sensory neuron excitability, mediated at least in part by modulation of TRP channel sensitivity.

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“…Solutions of the tested compounds were applied using a rapid perfusion system (Mayer et al 1989) consisting of an array of ten parallel quartz-glass tubes, each approximately 400 μm in diameter. Tubes were positioned in the vicinity of the recorded cells and the flow of various solutions was switched on/off under microcomputer control (Dittert et al 1998). A complete change of the solution around the cell could be achieved in 30 to 60 ms. For signal recording and data evaluation, an Axon Instruments Digidata 1320A digitizer and pClamp9 software package were used (Axon Instruments, Foster City, CA).…”

Section: Experimental Assaymentioning

confidence: 99%

Cholinergic properties of new 7-methoxytacrine-donepezil derivatives

Šepsová

Karasová²,

Tobin³

et al. 2015

gpb

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Abstract. Organophosphorus nerve agents inhibit acetylcholinesterase (AChE) which causes the breakdown of the transmitter acetylcholine (ACh) in the synaptic cleft. Overstimulation of cholinergic receptors (muscarinic and nicotinic) by excessive amounts of ACh causes several health problems and may even cause death. Reversible AChE inhibitors play an important role in prophylaxis against nerve agents. The presented study investigated whether 7-methoxytacrine (7-MEOTA) and 7-MEOTAdonepezil derivatives can act as central and peripheral reversible AChE inhibitors and simultaneously antagonize muscarinic and nicotinic receptors. The possible mechanism of action was studied on cell cultures (patch clamp technique, calcium mobilization assay) and on isolated smooth muscle tissue (contraction study). Furthermore, the kinetics of the compounds was also examined. CNS availability was predicted by determining the passive blood-brain barrier penetration estimated via a modified PAMPA assay. In conclusion, this study provides promising evidence that the new synthesized 7-ME-OTA-donepezil derivatives have the desired anticholinergic effect; they can inhibit AChE, and nicotinic and muscarinic receptors in the micromolar range. Furthermore, they seem to penetrate readily into the CNS. However, their real potency and benefit must be verified by in vivo experiments.

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A technique for fast application of heated solutions of different composition to cultured neurones

Cited by 72 publications

References 11 publications

A Key Role for gp130 Expressed on Peripheral Sensory Nerves in Pathological Pain

A Key Role for gp130 Expressed on Peripheral Sensory Nerves in Pathological Pain

Inhibitor κB Kinase β Deficiency in Primary Nociceptive Neurons Increases TRP Channel Sensitivity

Cholinergic properties of new 7-methoxytacrine-donepezil derivatives

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