دورية أكاديمية
Opioid Analgesic as a Positive Allosteric Modulator of Acid-Sensing Ion Channels
| العنوان: | Opioid Analgesic as a Positive Allosteric Modulator of Acid-Sensing Ion Channels |
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| المؤلفون: | Dmitry I. Osmakov, Lyudmila V. Onoprienko, Aleksandr P. Kalinovskii, Sergey G. Koshelev, Vasiliy N. Stepanenko, Yaroslav A. Andreev, Sergey A. Kozlov |
| المصدر: | International Journal of Molecular Sciences, Vol 25, Iss 3, p 1413 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | opioid peptide, acid-sensing ion channels, electrophysiology, positive allosteric modulation, ASIC pharmacology, analgesic peptide, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Tafalgin (Taf) is a tetrapeptide opioid used in clinical practice in Russia as an analgesic drug for subcutaneous administration as a solution (4 mg/mL; concentration of 9 mM). We found that the acid-sensing ion channels (ASICs) are another molecular target for this molecule. ASICs are proton-gated sodium channels that mediate nociception in the peripheral nervous system and contribute to fear and learning in the central nervous system. Using electrophysiological methods, we demonstrated that Taf could increase the integral current through heterologically expressed ASIC with half-maximal effective concentration values of 0.09 mM and 0.3 mM for rat and human ASIC3, respectively, and 1 mM for ASIC1a. The molecular mechanism of Taf action was shown to be binding to the channel in the resting state and slowing down the rate of desensitization. Taf did not compete for binding sites with both protons and ASIC3 antagonists, such as APETx2 and amiloride (Ami). Moreover, Taf and Ami together caused an unusual synergistic effect, which was manifested itself as the development of a pronounced second desensitizing component. Thus, the ability of Taf to act as a positive allosteric modulator of these channels could potentially cause promiscuous effects in clinical practice. This fact must be considered in patients’ treatment. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| العلاقة: | https://www.mdpi.com/1422-0067/25/3/1413Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms25031413 |
| الوصول الحر: | https://doaj.org/article/23f362f711884a8887f22259b01696ccTest |
| رقم الانضمام: | edsdoj.23f362f711884a8887f22259b01696cc |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms25031413 |