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 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.

中文翻译：

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离子通道TRPV1的肽阻滞剂在热刺激模型中显示出长时间的镇痛作用。

摘要

离子通道TRPV1是疼痛和炎性刺激的最重要整合剂之一，被认为是治疗疼痛状况的有希望的治疗靶标。在这项工作中，我们在“热板”测试中对海葵异丝桃属植物Kunitz型肽的重组类似物的镇痛作用进行了比较研究。毒液：APHC1-TRPV1的调节剂和HCRG21-TRPV1的完全阻滞剂。生物学测试的结果表明，尽管完全阻断剂HCRG21具有50％有效浓度的TRPV1抑制作用，但在肌肉内给药时具有与APHC1相同的镇痛能力，并保持13 h的观察时间。肌肉注射APHC1的镇痛效果为0.1 mg / kg，在5分钟内迅速发展，但持续3 h。肽的药效学特性差异与结合TRPV1的不同机制非常吻合。