Peptide Blocker of Ion Channel TRPV1 Exhibits a Long Analgesic Effect in the Heat Stimulation Model
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HEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
Peptide Blocker of Ion Channel TRPV1 Exhibits a Long Analgesic Effect in the Heat Stimulation Model O. V. Sintsovaa, V. A. Palikovb, Y. A. Palikovab, A. A. Klimovicha, I. N. Gladkikha, Y. A. Andreevc,d, M. M. Monastyrnayaa, E. P. Kozlovskayaa, I. A. Dyachenkob, S. A. Kozlovc, and E. V. Leychenkoa,* Presented by Academician V.A. Stonik Received December 26, 2019; revised February 20, 2020; accepted March 6, 2020
Abstract—The ion channel TRPV1, which is one of the most important integrators of pain and inflammatory stimuli, is considered a promising therapeutic target in the treatment of pain conditions. In this work, we performed a comparative study of the analgesic effect in the “hot plate” test of recombinant analogues of Kunitztype peptides from the sea anemone Heteractis crispa venom: APHC1—modulator of TRPV1 and HCRG21—a full blocker of TRPV1. As a result of biological tests, it was shown that the full blocker HCRG21, despite the higher value of 50% effective concentration of TRPV1 inhibition, had an equal analgesic ability with the APHC1 upon intramuscular administration and retained it for 13 h of observation. The analgesic effect of APHC1 at a dose of 0.1 mg/kg when administered intramuscularly developed very quickly in 5 min but lasted 3 h. The differences in the pharmacodynamic profile of the peptides are in good agreement with different mechanisms of binding to TRPV1. Keywords: sea anemone, Heteractis crispa, TRPV1, nociception, analgesia DOI: 10.1134/S1607672920030096
Currently, ion channels are promising therapeutic targets for designing new-generation selective drugs. Elucidation of the mechanisms of their functioning in health and disease remains a relevant task of biochemistry, the solution of which is impossible without using compounds of various chemical nature that can specifically interact with these proteins and, if possible, have different effects. A targeted search for new ionchannel ligands as candidates for drug development is of constant scientific interest, both for developing a methodology for basic and applied research and for selecting the safest and most effective drug. The TRPV1 channel (transient receptor potential vanilloid type 1) is one of the most important integrators of pain and inflammatory stimuli and is consida Elyakov
Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, Vladivostok, Russia b Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow oblast, Russia c Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia d Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russia *e-mail: [email protected]
ered a therapeutic target in the treatment of pain conditions of various etiologies. In mammals, it is responsible primarily for thermoregulation and transmission of pain signals from the periphery to the brain. As a molecular sensor, it reco
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