دورية أكاديمية
Interaction of α9α10 Nicotinic Receptors With Peptides and Proteins From Animal Venoms
العنوان: | Interaction of α9α10 Nicotinic Receptors With Peptides and Proteins From Animal Venoms |
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المؤلفون: | Victor Tsetlin, Yves Haufe, Valentina Safronova, Dmitriy Serov, PranavKumar Shadamarshan, Lina Son, Irina Shelukhina, Denis Kudryavtsev, Elena Kryukova, Igor Kasheverov, Annette Nicke, Yuri Utkin |
المصدر: | Frontiers in Cellular Neuroscience, Vol 15 (2021) |
بيانات النشر: | Frontiers Media S.A., 2021. |
سنة النشر: | 2021 |
المجموعة: | LCC:Neurosciences. Biological psychiatry. Neuropsychiatry |
مصطلحات موضوعية: | nicotinic acetylcholine receptor, α9α10 subtype, Xenopus laevis oocytes, α–neurotoxin, α-conotoxin, granulocytes, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
الوصف: | Unlike most neuronal nicotinic acetylcholine receptor (nAChR) subunits, α7, α9, and α10 subunits are able to form functional homo- or heteromeric receptors without any β subunits. While the α7 subtype is widely distributed in the mammalian brain and several peripheral tissues, α9 and α9α10 nAChRs are mainly found in the cochlea and immune cells. α-Conotoxins that specifically block the α9α10 receptor showed anti-nociceptive and anti-hyperalgesic effects in animal models. Hence, this subtype is considered a drug target for analgesics. In contrast to the α9α10-selective α-conotoxins, the three-finger toxin α-bungarotoxin inhibits muscle-type and α7 nAChRs in addition to α9α10 nAChRs. However, the selectivity of α-neurotoxins at the α9α10 subtype was less intensively investigated. Here, we compared the potencies of α-conotoxins and α-neurotoxins at the human α9α10 nAChR by two-electrode voltage clamp analysis upon expression in Xenopus oocytes. In addition, we analyzed effects of several α9α10-selective α-conotoxins on mouse granulocytes from bone marrow to identify possible physiological functions of the α9α10 nAChR subtype in these cells. The α-conotoxin-induced IL-10 release was measured upon LPS-stimulation. We found that α-conotoxins RgIA, PeIA, and Vc1.1 enhance the IL-10 expression in granulocytes which might explain the known anti-inflammatory and associated analgesic activities of α9α10-selective α-conotoxins. Furthermore, we show that two long-chain α-neurotoxins from the cobra Naja melanoleuca venom that were earlier shown to bind to muscle-type and α7 nAChRs, also inhibit the α9α10 subtype at nanomolar concentrations with one of them showing a significantly slower dissociation from this receptor than α-bungarotoxin. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1662-5102 |
Relation: | https://www.frontiersin.org/articles/10.3389/fncel.2021.765541/full; https://doaj.org/toc/1662-5102 |
DOI: | 10.3389/fncel.2021.765541 |
URL الوصول: | https://doaj.org/article/ddee6ebe968d4ca3b82ed22a5d5b98d9 |
رقم الأكسشن: | edsdoj.6ebe968d4ca3b82ed22a5d5b98d9 |
قاعدة البيانات: | Directory of Open Access Journals |
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