Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development

Abstract

The transient receptor potential vanilloid 1 (TRPV1) ion channel plays an important role in the peripheral nociceptive pathway. TRPV1 is a polymodal receptor that can be activated by multiple types of ligands and painful stimuli, such as noxious heat and protons, and contributes to various acute and chronic pain conditions. Therefore, TRPV1 is emerging as a novel therapeutic target for the treatment of various pain conditions. Notably, various peptides isolated from venomous animals potently and selectively control the activation and inhibition of TRPV1 by binding to its outer pore region. This review will focus on the mechanisms by which venom-derived peptides interact with this portion of TRPV1 to control receptor functions and how these mechanisms can drive the development of new types of analgesics.

Diversity analysis of sea anemone peptide toxins in different tissues of Heteractis crispa based on transcriptomics

“…Kunitz-type peptides block ion channels and are anti-inflammatory 73 . Kunitz-type peptides in sea anemones affect TRPV and type II Kv channels 74 – 76 . The ShPI-1 belongs to the Kunitz-type peptide, which is derived from the sea anemone Stichodactyla helianthus 77 – 79 .…”

“…The first Kunitz-type representative bovine pancreatic trypsin inhibitor (BPTI) is a serine protease inhibitor resisting inflammatory responses 135 , 136 . In sea anemones, Kunitz-type peptides act on TRPV1 and Kv channels 29 , 74 , 75 , indirect TRPV1 activation contributes to EGF receptor/PLA2/arachidonic acid/lipoxygenase pathway, resulting in Kunitz-type peptides regulating TRPV1 channel activity 41 , 137 . APHC1-3 is earlier shown to possess a unique property of inhibiting of the pain vanilloid receptor TRPV1 in vitro and providing the analgesic effects in vivo in addition to their trypsin inhibitory activity 76 .…”

The proteotranscriptomic characterization of venom in the white seafanEunicella singulariselucidates the evolution of Octocorallia arsenal

“…Among them, Kunitz-like peptides are frequently found in venoms [55] where they can act as inhibitors of several endogenous and exogenous proteases [56] but also show neurotoxic and neuromodulatory activity on a variety of receptors and ion channels [57,58], sometimes with multimodal action [56,58]. Kunitz-like toxins that bind ion channels can be used to paralyze prey and are being extensively studied for their analgesic and neuroprotective properties [59][60][61][62]. Our HMM search revealed the occurrence of two Kunitz-like toxins.…”