“…As an efficient defensive strategy, toxin-induced TRPV1 activation has been identified in several venomous animals [12][13][14]21,22]. The Chinese bird spider (Ornithoctonus huwena) exploits its bivalent toxin, DkTx, which results in the formation of a stable complex with the TRPV1's outer pore that leads to relentless channel activation and severe pain behavior [14].…”
Section: Discussionmentioning
confidence: 99%
“…It was found that centipede venom could reduce the heat activation threshold of the TRPV1 channel and activate TRPV1 at mammals' physiological body temperatures [12]. In addition, scorpion venom could also target the TRPV1 channel to elicit intense pain in the mildly acidic (pH 6.5) venom environment [21]. Caterpillar venoms are a well-known pain-producing chemical punch.…”
Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense heat, edema, erythema, and pruritus. However, there is little functional evidence to indicate a potential mechanism. In this study, we analyzed the biological characteristics of the crude venom from the larval stage of Latoia consocia living in South-West China. Intraplantar injection of the venom into the hind paws of mice induced severe acute pain behaviors in wild type (WT) mice; the responses were much reduced in TRPV1-deficit (TRPV1 KO) mice. The TRPV1-specific inhibitor, capsazepine, significantly attenuated the pain behaviors. Furthermore, the crude venom evoked strong calcium signals in the dorsal root ganglion (DRG) neurons of WT mice but not those of TRPV1 KO mice. Among the pain-related ion channels we tested, the crude venom only activated the TRPV1 channel. To better understand the venom components, we analyzed the transcriptome of the L. consocia sebaceous gland region. Our study suggests that TRPV1 serves as a primary nociceptor in caterpillar-induced pain and forms the foundation for elucidating the pain-producing mechanism.
“…As an efficient defensive strategy, toxin-induced TRPV1 activation has been identified in several venomous animals [12][13][14]21,22]. The Chinese bird spider (Ornithoctonus huwena) exploits its bivalent toxin, DkTx, which results in the formation of a stable complex with the TRPV1's outer pore that leads to relentless channel activation and severe pain behavior [14].…”
Section: Discussionmentioning
confidence: 99%
“…It was found that centipede venom could reduce the heat activation threshold of the TRPV1 channel and activate TRPV1 at mammals' physiological body temperatures [12]. In addition, scorpion venom could also target the TRPV1 channel to elicit intense pain in the mildly acidic (pH 6.5) venom environment [21]. Caterpillar venoms are a well-known pain-producing chemical punch.…”
Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense heat, edema, erythema, and pruritus. However, there is little functional evidence to indicate a potential mechanism. In this study, we analyzed the biological characteristics of the crude venom from the larval stage of Latoia consocia living in South-West China. Intraplantar injection of the venom into the hind paws of mice induced severe acute pain behaviors in wild type (WT) mice; the responses were much reduced in TRPV1-deficit (TRPV1 KO) mice. The TRPV1-specific inhibitor, capsazepine, significantly attenuated the pain behaviors. Furthermore, the crude venom evoked strong calcium signals in the dorsal root ganglion (DRG) neurons of WT mice but not those of TRPV1 KO mice. Among the pain-related ion channels we tested, the crude venom only activated the TRPV1 channel. To better understand the venom components, we analyzed the transcriptome of the L. consocia sebaceous gland region. Our study suggests that TRPV1 serves as a primary nociceptor in caterpillar-induced pain and forms the foundation for elucidating the pain-producing mechanism.
“…(b) Die Disulfidbrücken verbinden eine alpha‐Helix mit zwei beta‐Strängen zu einer kompakten Struktur. Entscheidend für die Bindung an den Schmerzrezeptor ist das Lysin an Position 23 (grün) [Abbildungen: (a) nach , (b) mit freundlicher Genehmigung von Jie Zheng, University of California (Davis/USA)].…”
Section: Legendär Schmerzhaftunclassified
“…Jetzt kann das Toxin BmP01 den Kanal aktivieren, indem es ein Proton nachahmt. Dazu bildet es eine Salzbrücke zu E649 aus [Abbildung nach ].…”
Der Stich des Mandschurei‐Skorpions löst an der Einstichstelle starke Schmerzen aus und setzt so dessen Feinde schachmatt. Die Schmerzen erzeugt ein Peptidtoxin, das an einen Schmerzrezeptor bindet und dabei synergistisch mit Protonen aus dem sauren Giftcocktail wirkt. Auf diese Weise wird der Schmerzrezeptor so stark aktiviert, wie es sonst nur durch eine extreme Ansäuerung des Gewebes zu erreichen wäre.
“…This toxin, found in the venom of Mesobuthus martensii , has a typical inhibitory cysteine knot (ICK) motif structure with three disulfide bonds (1–4, 2–5 and 3–6) stabilizing a compact and rigid protein fold ( Figure 4 ) [ 58 , 59 ]. Within the vast ICK toxins family, BmP01 is further sub-classified as part of the a-KTX8 toxins subgroup with whom it shares similar topology and sequence features [ 60 , 61 ].…”
Beyond providing evolutionary advantages, venoms offer unique research tools, as they were developed to target functionally important proteins and pathways. As a key pain receptor in the nociceptive pathway, transient receptor potential vanilloid 1 (TRPV1) of the TRP superfamily has been shown to be a target for several toxins, as a way of producing pain to deter predators. Importantly, TRPV1 is involved in thermoregulation, inflammation, and acute nociception. As such, toxins provide tools to understand TRPV1 activation and modulation, a critical step in advancing pain research and the development of novel analgesics. Indeed, the phytotoxin capsaicin, which is the spicy chemical in chili peppers, was invaluable in the original cloning and characterization of TRPV1. The unique properties of each subsequently characterized toxin have continued to advance our understanding of functional, structural, and biophysical characteristics of TRPV1. By building on previous reviews, this work aims to provide a comprehensive summary of the advancements made in TRPV1 research in recent years by employing animal toxins, in particular DkTx, RhTx, BmP01, Echis coloratus toxins, APHCs and HCRG21. We examine each toxin’s functional aspects, behavioral effects, and structural features, all of which have contributed to our current knowledge of TRPV1. We additionally discuss the key features of TRPV1’s outer pore domain, which proves to be the target of the currently discussed toxins.
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