Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia
Transient receptor potential vanilloid 1 receptors (TRPV1) play a significant physiological role. The study of novel TRPV1 agonists and antagonists is essential. Here, we report on the characterization of polypeptide antagonists of TRPV1 based on in vitro and in vivo experiments. We evaluated the ab...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2013-12-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/11/12/5100 |
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| author | Yaroslav A. Andreev Sergey A. Kozlov Yuliya V. Korolkova Igor A. Dyachenko Dmitrii A. Bondarenko Denis I. Skobtsov Arkadii N. Murashev Polina D. Kotova Olga A. Rogachevskaja Natalia V. Kabanova Stanislav S. Kolesnikov Eugene V. Grishin |
| author_facet | Yaroslav A. Andreev Sergey A. Kozlov Yuliya V. Korolkova Igor A. Dyachenko Dmitrii A. Bondarenko Denis I. Skobtsov Arkadii N. Murashev Polina D. Kotova Olga A. Rogachevskaja Natalia V. Kabanova Stanislav S. Kolesnikov Eugene V. Grishin |
| author_sort | Yaroslav A. Andreev |
| collection | DOAJ |
| description | Transient receptor potential vanilloid 1 receptors (TRPV1) play a significant physiological role. The study of novel TRPV1 agonists and antagonists is essential. Here, we report on the characterization of polypeptide antagonists of TRPV1 based on in vitro and in vivo experiments. We evaluated the ability of APHC1 and APHC3 to inhibit TRPV1 using the whole-cell patch clamp approach and single cell Ca2+ imaging. In vivo tests were performed to assess the biological effects of APHC1 and APHC3 on temperature sensation, inflammation and core body temperature. In the electrophysiological study, both polypeptides partially blocked the capsaicin-induced response of TRPV1, but only APHC3 inhibited acid-induced (pH 5.5) activation of the receptor. APHC1 and APHC3 showed significant antinociceptive and analgesic activity in vivo at reasonable doses (0.01–0.1 mg/kg) and did not cause hyperthermia. Intravenous administration of these polypeptides prolonged hot-plate latency, blocked capsaicin- and formalin-induced behavior, reversed CFA-induced hyperalgesia and produced hypothermia. Notably, APHC3’s ability to inhibit the low pH-induced activation of TRPV1 resulted in a reduced behavioural response in the acetic acid-induced writhing test, whereas APHC1 was much less effective. The polypeptides APHC1 and APHC3 could be referred to as a new class of TRPV1 modulators that produce a significant analgesic effect without hyperthermia. |
| first_indexed | 2024-04-11T10:59:31Z |
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| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T10:59:31Z |
| publishDate | 2013-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-5aaa2041c8f74b2c940ee7ba1423b5992022-12-22T04:28:40ZengMDPI AGMarine Drugs1660-33972013-12-0111125100511510.3390/md11125100md11125100Polypeptide Modulators of TRPV1 Produce Analgesia without HyperthermiaYaroslav A. Andreev0Sergey A. Kozlov1Yuliya V. Korolkova2Igor A. Dyachenko3Dmitrii A. Bondarenko4Denis I. Skobtsov5Arkadii N. Murashev6Polina D. Kotova7Olga A. Rogachevskaja8Natalia V. Kabanova9Stanislav S. Kolesnikov10Eugene V. Grishin11Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya Str., Moscow 117997, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya Str., Moscow 117997, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya Str., Moscow 117997, RussiaBranch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki ave., Pushchino 142290, Moscow Region, RussiaBranch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki ave., Pushchino 142290, Moscow Region, RussiaBranch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki ave., Pushchino 142290, Moscow Region, RussiaBranch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 6 Nauki ave., Pushchino 142290, Moscow Region, RussiaInstitute of Cell Biophysics, Russian Academy of Sciences, 3 Institutskaya Str., Pushchino 142290, Moscow Region, RussiaInstitute of Cell Biophysics, Russian Academy of Sciences, 3 Institutskaya Str., Pushchino 142290, Moscow Region, RussiaInstitute of Cell Biophysics, Russian Academy of Sciences, 3 Institutskaya Str., Pushchino 142290, Moscow Region, RussiaInstitute of Cell Biophysics, Russian Academy of Sciences, 3 Institutskaya Str., Pushchino 142290, Moscow Region, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya Str., Moscow 117997, RussiaTransient receptor potential vanilloid 1 receptors (TRPV1) play a significant physiological role. The study of novel TRPV1 agonists and antagonists is essential. Here, we report on the characterization of polypeptide antagonists of TRPV1 based on in vitro and in vivo experiments. We evaluated the ability of APHC1 and APHC3 to inhibit TRPV1 using the whole-cell patch clamp approach and single cell Ca2+ imaging. In vivo tests were performed to assess the biological effects of APHC1 and APHC3 on temperature sensation, inflammation and core body temperature. In the electrophysiological study, both polypeptides partially blocked the capsaicin-induced response of TRPV1, but only APHC3 inhibited acid-induced (pH 5.5) activation of the receptor. APHC1 and APHC3 showed significant antinociceptive and analgesic activity in vivo at reasonable doses (0.01–0.1 mg/kg) and did not cause hyperthermia. Intravenous administration of these polypeptides prolonged hot-plate latency, blocked capsaicin- and formalin-induced behavior, reversed CFA-induced hyperalgesia and produced hypothermia. Notably, APHC3’s ability to inhibit the low pH-induced activation of TRPV1 resulted in a reduced behavioural response in the acetic acid-induced writhing test, whereas APHC1 was much less effective. The polypeptides APHC1 and APHC3 could be referred to as a new class of TRPV1 modulators that produce a significant analgesic effect without hyperthermia.http://www.mdpi.com/1660-3397/11/12/5100sea anemoneanalgesic polypeptide APHCTRPV1 receptoranimal modelstemperature regulationnociceptioninflammation |
| spellingShingle | Yaroslav A. Andreev Sergey A. Kozlov Yuliya V. Korolkova Igor A. Dyachenko Dmitrii A. Bondarenko Denis I. Skobtsov Arkadii N. Murashev Polina D. Kotova Olga A. Rogachevskaja Natalia V. Kabanova Stanislav S. Kolesnikov Eugene V. Grishin Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia Marine Drugs sea anemone analgesic polypeptide APHC TRPV1 receptor animal models temperature regulation nociception inflammation |
| title | Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia |
| title_full | Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia |
| title_fullStr | Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia |
| title_full_unstemmed | Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia |
| title_short | Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia |
| title_sort | polypeptide modulators of trpv1 produce analgesia without hyperthermia |
| topic | sea anemone analgesic polypeptide APHC TRPV1 receptor animal models temperature regulation nociception inflammation |
| url | http://www.mdpi.com/1660-3397/11/12/5100 |
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