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Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel.

Hakim MA, Jiang W, Luo L, Li B, Yang S, Song Y, Lai R - Toxins (Basel) (2015)

Bottom Line: Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1.These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1.To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. hakeem.geb.ru@gmail.com.

ABSTRACT
The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation.

No MeSH data available.


Related in: MedlinePlus

BmP01 activated TRPV1 channel. (A) Application of BmP01 at the concentrations of 1 µM, 10 µM, 100 µM, 500 µM and 1 mM showed the increasing activity with higher concentration to activate TRPV1 currents. Along with Capsaicin, proton and 2APB, 500 µM of BmP01 completely activates the TRPV1 channel; (B) Concentration—response yielded an EC50 of 131.8 ± 49.1 µM BmP01 (n = 10); (C) In HEK293T cells, negative for TRPV1 channel, BmP01 and capsaicin did not evoke the currents, whereas only proton induced some currents; (D) In contrast, BmP01 and capsaicin evoked the currents in HEK293T cells with over-expressed TRPV1 channels.
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toxins-07-03671-f005: BmP01 activated TRPV1 channel. (A) Application of BmP01 at the concentrations of 1 µM, 10 µM, 100 µM, 500 µM and 1 mM showed the increasing activity with higher concentration to activate TRPV1 currents. Along with Capsaicin, proton and 2APB, 500 µM of BmP01 completely activates the TRPV1 channel; (B) Concentration—response yielded an EC50 of 131.8 ± 49.1 µM BmP01 (n = 10); (C) In HEK293T cells, negative for TRPV1 channel, BmP01 and capsaicin did not evoke the currents, whereas only proton induced some currents; (D) In contrast, BmP01 and capsaicin evoked the currents in HEK293T cells with over-expressed TRPV1 channels.

Mentions: According to the findings from DRG neurons and animal behavior tests, BmP01 displayed a similar pharmacological response with capsaicin, the well-known agonist of TRPV1. We were interested in the investigation of the molecular interaction between BmP01 and TRPV1. Thus, electrophysiological tests on transient transfected TRPV1 were performed. According to the recordings from transient transfected mTRPV1 expressed on HEK293T cells, in electrophysiology, BmP01 with the concentration of 1 µM, 10 µM, 100 µM, 500 µM and 1 mM was applied and found to activate the mTRPV1 channel in a dose dependent manner. Five hundred micromoles of BmP01 along with capsaicin, proton and 2APB potently activated TRPV1 (Figure 5A). Determination of concentration–response relationship yielded an EC50 of 131.8 ± 49.1 µM on TRPV1 channel currents (Figure 5B). To our knowledge, HEK293T cells have been reported to endogenously express acid-sensing ion channels (ASICs) [39]. In order to check whether BmP01-induced currents were caused by the activation of ASICs, ramp method was used for comparing the toxin effects between TRPV1-expressed and native HEK293T cells. In native HEK293T cells, BmP01 as well as capsaicin did not evoke currents, but proton evoked current to some extent due to the endogenous ASICs (Figure 5C). Because of the expression level of endogenous ASICs, the currents evoked by proton hardly influenced the whole-cell currents in TRPV1-expressed cells. Thus, the same experiment carried out on TRPV1-expressed cells determined that BmP01-induced currents were elicited from TRPV1 channels (Figure 5D). These observations reveal that BmP01 acts as the agonist of mTRPV1 and consequently induces pain in the similar molecular pathway of capsaicin.


Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel.

Hakim MA, Jiang W, Luo L, Li B, Yang S, Song Y, Lai R - Toxins (Basel) (2015)

BmP01 activated TRPV1 channel. (A) Application of BmP01 at the concentrations of 1 µM, 10 µM, 100 µM, 500 µM and 1 mM showed the increasing activity with higher concentration to activate TRPV1 currents. Along with Capsaicin, proton and 2APB, 500 µM of BmP01 completely activates the TRPV1 channel; (B) Concentration—response yielded an EC50 of 131.8 ± 49.1 µM BmP01 (n = 10); (C) In HEK293T cells, negative for TRPV1 channel, BmP01 and capsaicin did not evoke the currents, whereas only proton induced some currents; (D) In contrast, BmP01 and capsaicin evoked the currents in HEK293T cells with over-expressed TRPV1 channels.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591660&req=5

toxins-07-03671-f005: BmP01 activated TRPV1 channel. (A) Application of BmP01 at the concentrations of 1 µM, 10 µM, 100 µM, 500 µM and 1 mM showed the increasing activity with higher concentration to activate TRPV1 currents. Along with Capsaicin, proton and 2APB, 500 µM of BmP01 completely activates the TRPV1 channel; (B) Concentration—response yielded an EC50 of 131.8 ± 49.1 µM BmP01 (n = 10); (C) In HEK293T cells, negative for TRPV1 channel, BmP01 and capsaicin did not evoke the currents, whereas only proton induced some currents; (D) In contrast, BmP01 and capsaicin evoked the currents in HEK293T cells with over-expressed TRPV1 channels.
Mentions: According to the findings from DRG neurons and animal behavior tests, BmP01 displayed a similar pharmacological response with capsaicin, the well-known agonist of TRPV1. We were interested in the investigation of the molecular interaction between BmP01 and TRPV1. Thus, electrophysiological tests on transient transfected TRPV1 were performed. According to the recordings from transient transfected mTRPV1 expressed on HEK293T cells, in electrophysiology, BmP01 with the concentration of 1 µM, 10 µM, 100 µM, 500 µM and 1 mM was applied and found to activate the mTRPV1 channel in a dose dependent manner. Five hundred micromoles of BmP01 along with capsaicin, proton and 2APB potently activated TRPV1 (Figure 5A). Determination of concentration–response relationship yielded an EC50 of 131.8 ± 49.1 µM on TRPV1 channel currents (Figure 5B). To our knowledge, HEK293T cells have been reported to endogenously express acid-sensing ion channels (ASICs) [39]. In order to check whether BmP01-induced currents were caused by the activation of ASICs, ramp method was used for comparing the toxin effects between TRPV1-expressed and native HEK293T cells. In native HEK293T cells, BmP01 as well as capsaicin did not evoke currents, but proton evoked current to some extent due to the endogenous ASICs (Figure 5C). Because of the expression level of endogenous ASICs, the currents evoked by proton hardly influenced the whole-cell currents in TRPV1-expressed cells. Thus, the same experiment carried out on TRPV1-expressed cells determined that BmP01-induced currents were elicited from TRPV1 channels (Figure 5D). These observations reveal that BmP01 acts as the agonist of mTRPV1 and consequently induces pain in the similar molecular pathway of capsaicin.

Bottom Line: Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1.These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1.To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. hakeem.geb.ru@gmail.com.

ABSTRACT
The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation.

No MeSH data available.


Related in: MedlinePlus