Analgesic Activity of Acid-Sensing Ion Channel 3 (ASIС3) Inhibitors: Sea Anemones Peptides Ugr9-1 and APETx2 versus Low Molecular Weight Compounds
Autor: | Dmitry I. Osmakov, Sergey A. Kozlov, Yulia A. Palikova, Sergey G. Koshelev, Yulia A. Logashina, Yaroslav A. Andreev, Ekaterina E. Maleeva, Victor A. Palikov, Igor A. Dyachenko |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Male
Nociception 0301 basic medicine Diclofenac Patch-Clamp Techniques Analgesic Pain Pharmaceutical Science acid-sensing ion channel Ugr 9-1 Inflammation Peptide Pharmacology Article pain relief Mice Xenopus laevis 03 medical and health sciences Acetic acid chemistry.chemical_compound Drug Discovery medicine Animals Humans toxin Pharmacology Toxicology and Pharmaceutics (miscellaneous) lcsh:QH301-705.5 Acid-sensing ion channel Ion channel Acetic Acid chemistry.chemical_classification Analgesics Biological Products APETx2 animal models Acid Sensing Ion Channels Disease Models Animal Sea Anemones 030104 developmental biology chemistry lcsh:Biology (General) Acid Sensing Ion Channel Blockers Hyperalgesia medicine.symptom Peptides Intramuscular injection medicine.drug |
Zdroj: | Marine Drugs, Vol 16, Iss 12, p 500 (2018) Marine Drugs Volume 16 Issue 12 |
ISSN: | 1660-3397 |
Popis: | Acid-sensing ion channel 3 (ASIC3) makes an important contribution to the development and maintenance of inflammatory and acid-induced pain. We compared different ASIC3 inhibitors (peptides from sea anemones (APETx2 and Ugr9-1) and nonpeptide molecules (sevanol and diclofenac)) in anti-inflammatory action and analgesic effects. All tested compounds had distinct effects on pH-induced ASIC3 current. APETx2 inhibited only transient current, whereas Ugr9-1 and sevanol decreased transient and sustained components of the current. The effect on mice was evaluated after administering an intramuscular injection in the acetic acid writhing pain model and the complete Freund&rsquo s adjuvant-induced thermal hyperalgesia/inflammation test. The bell-shaped dependence of the analgesic effect was observed for APETx2 in the acetic acid-induced writhing test, as well as for sevanol and peptide Ugr9-1 in the thermal hyperalgesia test. This dependence could be evidence of the nonspecific action of compounds in high doses. Compounds reducing both components of ASIC3 current produced more significant pain relief than APETx2, which is an effective inhibitor of a transient current only. Therefore, the comparison of the efficacy of ASIC3 inhibitors revealed the importance of ASIC3-sustained currents&rsquo inhibition for promotion of acidosis-related pain relief. |
Databáze: | OpenAIRE |
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