Sintsova O V, Palikov V A, Palikova Y A, Klimovich A A, Gladkikh I N, Andreev Y A, Monastyrnaya M M, Kozlovskaya E P, Dyachenko I A, Kozlov S A, Leychenko E V
Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, Vladivostok, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow oblast, Russia.
Dokl Biochem Biophys. 2020 Jul;493(1):215-217. doi: 10.1134/S1607672920030096. Epub 2020 Sep 7.
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 Kunitz-type 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.
离子通道TRPV1是疼痛和炎症刺激的最重要整合器之一，被认为是治疗疼痛病症的一个有前景的治疗靶点。在这项工作中，我们对来自海葵卷曲异海葵毒液的Kunitz型肽的重组类似物：TRPV1的调节剂APHC1和TRPV1的完全阻断剂HCRG21，在“热板”试验中的镇痛效果进行了比较研究。生物学测试结果表明，尽管TRPV1抑制的50%有效浓度值较高，但完全阻断剂HCRG21在肌肉注射时与APHC1具有同等的镇痛能力，并且在13小时的观察期内保持该能力。APHC1以0.1mg/kg的剂量肌肉注射时，镇痛效果在5分钟内迅速显现，但持续3小时。这些肽的药效学特征差异与它们与TRPV1的不同结合机制高度吻合。
