LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 4 of total 4

Search options

  1. Article ; Online: Clotrimazole-Based Modulators of the TRPM3 Ion Channel Reveal Narrow Structure-Activity Relationship.

    Kahler, Jan Pascal / Aloi, Vincenzo Davide / Miedes Aliaga, Julia / Kerselaers, Sara / Voets, Thomas / Vriens, Joris / Verhelst, Steven H L / Barniol-Xicota, Marta

    ACS chemical biology

    2023  Volume 18, Issue 3, Page(s) 456–464

    Abstract: TRPM3 is an ion channel that is highly expressed in nociceptive neurons and plays a key role in pain perception. In the presence of the endogenous TRPM3 ligand, pregnenolone sulfate (PS), the antifungal compound clotrimazole (Clt) augments ... ...

    Abstract TRPM3 is an ion channel that is highly expressed in nociceptive neurons and plays a key role in pain perception. In the presence of the endogenous TRPM3 ligand, pregnenolone sulfate (PS), the antifungal compound clotrimazole (Clt) augments Ca
    MeSH term(s) Humans ; Clotrimazole/pharmacology ; TRPM Cation Channels/metabolism ; Pain ; Structure-Activity Relationship
    Chemical Substances Clotrimazole (G07GZ97H65) ; TRPM Cation Channels ; TRPM3 protein, human
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/acschembio.2c00672
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain.

    Aloi, Vincenzo Davide / Pinto, Sílvia João Poseiro Coutinho / Van Bree, Rita / Luyten, Katrien / Voets, Thomas / Vriens, Joris

    Pain

    2023  Volume 164, Issue 9, Page(s) 2060–2069

    Abstract: Abstract: Chemotherapy-induced peripheral neuropathic pain (CIPNP) is an adverse effect observed in up to 80% of patients of cancer on treatment with cytostatic drugs including paclitaxel and oxaliplatin. Chemotherapy-induced peripheral neuropathic pain ...

    Abstract Abstract: Chemotherapy-induced peripheral neuropathic pain (CIPNP) is an adverse effect observed in up to 80% of patients of cancer on treatment with cytostatic drugs including paclitaxel and oxaliplatin. Chemotherapy-induced peripheral neuropathic pain can be so severe that it limits dose and choice of chemotherapy and has significant negative consequences on the quality of life of survivors. Current treatment options for CIPNP are limited and unsatisfactory. TRPM3 is a calcium-permeable ion channel functionally expressed in peripheral sensory neurons involved in the detection of thermal stimuli. Here, we focus on the possible involvement of TRPM3 in acute oxaliplatin-induced mechanical allodynia and cold hypersensitivity. In vitro calcium microfluorimetry and whole-cell patch-clamp experiments showed that TRPM3 is functionally upregulated in both heterologous and homologous expression systems after acute (24 hours) oxaliplatin treatment, whereas the direct application of oxaliplatin was without effect. In vivo behavioral studies using an acute oxaliplatin model for CIPNP showed the development of cold and mechano hypersensitivity in control mice, which was lacking in TRPM3 deficient mice. In addition, the levels of protein ERK, a marker for neuronal activity, were significantly reduced in dorsal root ganglion neurons derived from TRPM3 deficient mice compared with control after oxaliplatin administration. Moreover, intraperitoneal injection of a TRPM3 antagonist, isosakuranetin, effectively reduced the oxaliplatin-induced pain behavior in response to cold and mechanical stimulation in mice with an acute form of oxaliplatin-induced peripheral neuropathy. In summary, TRPM3 represents a potential new target for the treatment of neuropathic pain in patients undergoing chemotherapy.
    MeSH term(s) Animals ; Mice ; Antineoplastic Agents/adverse effects ; Calcium/metabolism ; Hyperalgesia/chemically induced ; Hyperalgesia/drug therapy ; Neuralgia/chemically induced ; Neuralgia/drug therapy ; Neuralgia/metabolism ; Oxaliplatin/adverse effects ; TRPM Cation Channels
    Chemical Substances Antineoplastic Agents ; Calcium (SY7Q814VUP) ; Oxaliplatin (04ZR38536J) ; TRPM Cation Channels ; TRPM3 protein, mouse
    Language English
    Publishing date 2023-04-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000002906
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1158: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Mutations in the voltage-sensing domain affect the alternative ion permeation pathway in the TRPM3 channel.

    Held, Katharina / Gruss, Fabian / Aloi, Vincenzo Davide / Janssens, Annelies / Ulens, Chris / Voets, Thomas / Vriens, Joris

    The Journal of physiology

    2018  Volume 596, Issue 12, Page(s) 2413–2432

    Abstract: Key points: Mutagenesis at positively charged amino acids (arginines and lysines) (R1-R4) in the voltage-sensor domain (transmembrane segment (S) 4) of voltage-gated Na: Abstract: Transient receptor potential (TRP) channels are cationic channels ... ...

    Abstract Key points: Mutagenesis at positively charged amino acids (arginines and lysines) (R1-R4) in the voltage-sensor domain (transmembrane segment (S) 4) of voltage-gated Na
    Abstract: Transient receptor potential (TRP) channels are cationic channels involved in a broad array of functions, including homeostasis, motility and sensory functions. TRP channel subunits consist of six transmembrane segments (S1-S6), and form tetrameric channels with a central pore formed by the region encompassing S5 and S6. Recently, evidence was provided for the existence of an alternative ion permeation pathway in TRPM3, which allows large inward currents upon hyperpolarization independently of the central pore. However, very little knowledge is available concerning the localization of this alternative pathway in the native TRPM3 channel protein. Guided by sequence homology with Shaker K
    MeSH term(s) Amino Acid Sequence ; Amino Acids ; Animals ; Arginine/chemistry ; Arginine/genetics ; Arginine/metabolism ; HEK293 Cells ; Humans ; Ion Channel Gating ; Mice ; Mutagenesis, Site-Directed ; Mutation ; Protein Structure, Tertiary ; TRPM Cation Channels/chemistry ; TRPM Cation Channels/genetics ; TRPM Cation Channels/physiology
    Chemical Substances Amino Acids ; TRPM Cation Channels ; TRPM3 protein, mouse ; Arginine (94ZLA3W45F)
    Language English
    Publishing date 2018-04-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP274124
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.65: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Pharmacological properties of TRPM3 isoforms are determined by the length of the pore loop.

    Held, Katharina / Aloi, Vincenzo Davide / Freitas, Ana Cristina Nogueira / Janssens, Annelies / Segal, Andrei / Przibilla, Julia / Philipp, Stephan Ernst / Wang, Yu Tian / Voets, Thomas / Vriens, Joris

    British journal of pharmacology

    2020  Volume 179, Issue 14, Page(s) 3560–3575

    Abstract: Background and purpose: Transient receptor potential melastatin 3 (TRPM3) is a non-selective cation channel that plays a pivotal role in the peripheral nervous system as a transducer of painful heat signals. Alternative splicing gives rise to several ... ...

    Abstract Background and purpose: Transient receptor potential melastatin 3 (TRPM3) is a non-selective cation channel that plays a pivotal role in the peripheral nervous system as a transducer of painful heat signals. Alternative splicing gives rise to several TRPM3 variants. The functional consequences of these splice isoforms are poorly understood. Here, the pharmacological properties of TRPM3 variants arising from alternative splicing in the pore-forming region were compared.
    Experimental approach: Calcium microfluorimetry and patch clamp recordings were used to compare the properties of heterologously expressed TRPM3α1 (long pore variant) and TRPM3α2-α6 (short pore variants). Furthermore, site-directed mutagenesis was done to investigate the influence of the length of the pore loop on the channel function.
    Key results: All short pore loop TRPM3α variants (TRPM3α2-α6) were activated by the neurosteroid pregnenolone sulphate (PS) and by nifedipine, whereas the long pore loop variant TRPM3α1 was insensitive to either compound. In contrast, TRPM3α1 was robustly activated by clotrimazole, a compound that does not directly activate the short pore variants but potentiates their responses to PS. Clotrimazole-activated TRPM3α1 currents were largely insensitive to established TRPM3α2 antagonists and were only partially inhibited upon activation of the μ opioid receptor. Finally, by creating a set of mutant channels with pore loops of intermediate length, we showed that the length of the pore loop dictates differential channel activation by PS and clotrimazole.
    Conclusion and implications: Alternative splicing in the pore-forming region of TRPM3 defines the channel's pharmacological properties, which depend critically on the length of the pore-forming loop.
    Linked articles: This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc.
    MeSH term(s) Alternative Splicing ; Calcium/metabolism ; Clotrimazole ; Protein Isoforms/metabolism ; TRPM Cation Channels/metabolism
    Chemical Substances Protein Isoforms ; TRPM Cation Channels ; Clotrimazole (G07GZ97H65) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-08-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.15223
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uf I Zs.146: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top