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Start Over Creator Ladislav Vyklický

2. Calcium-dependent desensitization of vanilloid receptor TRPV1: a mechanism possibly involved in analgesia induced by topical application of capsaicin

Creator:
Ladislav Vyklický, Karolina Nováková-Toušová, Jan Benedikt, Abdul Samad, Filip Touška, and Viktorie Vlachová
Format:
print, bez média, and svazek
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, neurofyziologie, analgezie, neurophysiology, analgesia, vanilloid 1 receptors (TRPV1), capsaicin, topical application, desensitization, 14, and 612
Language:
English
Description:
The rationale for the topical application of capsaicin and other vanilloids in the treatment of pain is that such compounds selectively excite and subsequently desensitize nociceptive neurons. This desensitization is triggered by the activation of vanilloid receptors (TRPV1), which leads to an elevation in intracellular free Ca2+ levels. Depending on the vanilloid concentration and duration of exposure, the Ca2+ influx via TRPV1 desensitizes the channels themselves, which may represent not only a feedback mechanism protecting the cell from toxic Ca2+ overload, but also likely contributes to the analgesic effects of capsaicin. This review summarizes the current state of knowledge concerning the mechanisms that underlie the acute capsaicin-induced Ca2+-dependent desensitization of TRPV1 channels and explores to what extent they may contribute to capsaicin-induced analgesia. In view of the polymodal nature of TRPV1, we illustrate how the channels behave in their desensitized state when activated by other stimuli such as noxious heat or depolarizing voltages. We also show that the desensitized channel can be strongly reactivated by capsaicin at concentrations higher than those previously used to desensitize it. We provide a possible explanation for a high incidence of adverse effects of topical capsaicin and point to a need for more accurate clinical criteria for employing it as a reliable remedy., L. Vyklický, K. Nováková-Toušová, J. Benedikt, A. Samad, F. Touška, V. Vlachová., and Obsahuje bibliografii a bibliografické odkazy
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

3. Neurosteroid modulation of ionotropic glutamate receptors and excitatory synaptic transmission

Creator:
Miloslav Sedláček, Miloslav Kořínek, Miloš Petrovič, Cais, O., Adamusová, E., Hana Chodounská, and Ladislav Vyklický
Format:
print, bez média, and svazek
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, fyziologie, neurologie, physiology, neurology, N-methyl-D-aspartate receptor, AMPA receptor, glutamate receptor, EPSC, neurosteroid, allosteric modulation, 14, and 612
Language:
English
Description:
Ionotropic glutamate receptors function can be affected by neurosteroids, both positively and negatively. N-methyl-D-aspartate (NMDA) receptor responses to exogenously applied glutamate are potentiated or inhibited (depending on the receptor subunit composition) by pregnenolone sulphate (PS) and inhibited by pregnenolone sulphate (3α5βS). While PS effect is most pronounced when its application precedes that of glutamate, 3α5βS only binds to receptors already activated. Synaptically activated NMDA receptors are inhibited by 3α5βS, though to a lesser extent than those tonically activated by exogenous glutamate. PS, on the other hand, shows virtually no effect on any of the models of synaptically activated NMDA receptors. The site of neurosteroid action at the receptor molecule has not yet been identified, however, the experiments indicate that there are at least two distinct extracellularly located binding sites for PS mediating its potentiating and inhibitory effects respectively. Experiments with chimeric receptors revealed the importance of the extracellular loop connecting the third and the fourth transmembrane domain of the receptor NR2 subunit for the neurosteroid action, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors are inhibited by both PS and 3α5βS. These neurosteroids also affect AMPA receptors-mediated synaptic transmission, however, in a rather indirect way, through presynaptically located targets of action., M. Sedláček, M. Kořínek, M. Petrovič, O. Cais, E. Adamusová, H. Chodounská, L. Vyklický Jr., and Obsahuje bibliografii a bibliografické odkazy
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

4. Pregnenolone sulfate activates NMDA receptor channels

Creator:
Adamusová, E., Cais, O., Vyklický, V., Kudová, E., Hana Chodounská, Martin Horák, and Ladislav Vyklický
Format:
print
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, fyziologie, physiology, neurosteroids, N-methyl-D-aspartate receptor, pregnenolone sulfate, calcium imaging, recombinant receptors, 14, and 612
Language:
English
Description:
Pregnenolone sulfate (PS), an endogenously occurring neurosteroid, has been shown to modulate the activity of several neurotransmitter-gated channels, including the NMDA receptor (NMDAR). NMDARs are glutamate-gated ion channels involved in excitatory synaptic transmission, synaptic plasticity, and excitotoxicity. In this study, we analyzed the effects of PS on calcium signaling in cultured hippocampal neurons and HEK293 cells expressing NMDAR. The ce lls were loaded with the Ca 2+ sensor Fura-2. In agreement with previous electrophysiological experiments, PS potentiated the increases in intracellular Ca 2+ induced by an exogenous application of glutamate; however, PS also increased intracellular Ca 2+ in the absence of exogenous NMDA agonist. The agonist-independent effect of PS was induced in all neurons studied and in HEK293 cells expressing GluN1/GluN2A-B receptors in a neurosteroid-specific manner. We conclude that PS is an endogenous NMDA agonist that activates the GluN1/GluN2A-B receptors., E. Adamusová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

5. Suramin Affects Capsaicin Responses and Capsaicin-Noxious Heat Interactions in Rat Dorsal Root Ganglia Neurones

Creator:
Viktorie Vlachová, Alla Lyfenko, Ladislav Vyklický, and Orkand, R. K.
Format:
print, bez média, and svazek
Type:
article, studie, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, fyziologie člověka, human physiology, Dorsal root ganglia neurones, Vanilloid receptor, Capsaicin, Noxious heat, Whole-cell, 14, and 612
Language:
English
Description:
The effect of suramin, an inhibitor of G protein regulated signalling, was studied on the membrane currents induced by noxious heat and by capsaicin in cultured dorsal root ganglia neurones isolated from neonatal rats. Whole-cell responses induced by a heat ramp (24-52 °C) were little affected by suramin. The noxious heat-activated currents were synergistically facilitated in the presence of 0.3 µM capsaicin 13.2-fold and 6.3-fold at 40 °C and 50 °C, respectively. In 65% of neurones, the capsaicin-induced facilitation was inhibited by 10 µM suramin to 35±6 % and 53±6 % of control at 40 °C and 50 °C (S.E.M., n=15). Suramin 30 µM caused a significant increase in the membrane current produced by a nearly maximal dose (1 µM) of capsaicin over the whole recorded temperature range (2.4-fold at 25 °C and 1.2-fold at 48 °C). The results demonstrate that suramin differentially affects the interaction between capsaicin and noxious heat in DRG neurones and thus suggest that distinct transduction pathways may participate in vanilloid receptor activation mechanisms., V. Vlachová, A. Lyfenko, L. Vyklický, † R.K. Orkand., and Obsahuje bibliografii
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public