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The peptide Phα1β, from spider venom, acts as a TRPA1 channel antagonist with antinociceptive effects in mice.
Br J Pharmacol. 2017 01; 174(1):57-69.BJ

Abstract

BACKGROUND AND PURPOSE

Peptides from venomous animals have long been important for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide from the venom of the armed spider Phoneutria nigriventer, produces analgesia by blocking the TRPA1 channel.

EXPERIMENTAL APPROACH

Cultured rat dorsal root ganglion (DRG) neurons, human fetal lung fibroblasts (IMR90) or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), human TRPV1 (hTRPV1-HEK293) or human TRPV4 channels (hTRPV4-HEK293), were used for calcium imaging and electrophysiology. Nociceptive responses induced by TRPA1, TRPV1 or TRPV4 agonists or by bortezomib were investigated in mice.

KEY RESULTS

Phα1β selectively inhibited calcium responses and currents evoked by the TRPA1 agonist, allyl isothiocyanate (AITC), on hTRPA1-HEK293, IMR90 fibroblasts and DRG neurons. Phα1β did not affect calcium responses evoked by selective TRPV1 (capsaicin) or TRPV4 (GSK 1016790A) agonists on the various cell types. Intrathecal (i.t.) and intraplantar (i.pl.) administration of low doses of Phα1β (up to 300 pmol per paw) attenuated acute nociception and mechanical and cold hyperalgesia evoked by AITC (i.t. or i.pl.), without affecting responses produced by capsaicin or hypotonic solution. Notably, Phα1β abated the TRPA1-dependent neuropathic pain-like responses induced by bortezomib. In vitro and in vivo inhibition of TRPA1 by Phα1β was reproduced by a recombinant form of the peptide, CTK 01512-2.

CONCLUSIONS AND IMPLICATIONS

Phα1β and CTK 01512-2 selectively target TRPA1, but not other TRP channels. This specific action underlines the potential of Phα1β and CTK 01512-2 for pain treatment.

Authors+Show Affiliations

Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, Brazil. Departmento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Núcleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, Brazil.Núcleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, Brazil.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Departmento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27759880

Citation

Tonello, Raquel, et al. "The Peptide Phα1β, From Spider Venom, Acts as a TRPA1 Channel Antagonist With Antinociceptive Effects in Mice." British Journal of Pharmacology, vol. 174, no. 1, 2017, pp. 57-69.
Tonello R, Fusi C, Materazzi S, et al. The peptide Phα1β, from spider venom, acts as a TRPA1 channel antagonist with antinociceptive effects in mice. Br J Pharmacol. 2017;174(1):57-69.
Tonello, R., Fusi, C., Materazzi, S., Marone, I. M., De Logu, F., Benemei, S., Gonçalves, M. C., Coppi, E., Castro-Junior, C. J., Gomez, M. V., Geppetti, P., Ferreira, J., & Nassini, R. (2017). The peptide Phα1β, from spider venom, acts as a TRPA1 channel antagonist with antinociceptive effects in mice. British Journal of Pharmacology, 174(1), 57-69. https://doi.org/10.1111/bph.13652
Tonello R, et al. The Peptide Phα1β, From Spider Venom, Acts as a TRPA1 Channel Antagonist With Antinociceptive Effects in Mice. Br J Pharmacol. 2017;174(1):57-69. PubMed PMID: 27759880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The peptide Phα1β, from spider venom, acts as a TRPA1 channel antagonist with antinociceptive effects in mice. AU - Tonello,Raquel, AU - Fusi,Camilla, AU - Materazzi,Serena, AU - Marone,Ilaria M, AU - De Logu,Francesco, AU - Benemei,Silvia, AU - Gonçalves,Muryel C, AU - Coppi,Elisabetta, AU - Castro-Junior,Celio J, AU - Gomez,Marcus Vinicius, AU - Geppetti,Pierangelo, AU - Ferreira,Juliano, AU - Nassini,Romina, Y1 - 2016/11/28/ PY - 2015/11/13/received PY - 2016/09/07/revised PY - 2016/10/06/accepted PY - 2016/10/21/pubmed PY - 2017/11/7/medline PY - 2016/10/21/entrez SP - 57 EP - 69 JF - British journal of pharmacology JO - Br J Pharmacol VL - 174 IS - 1 N2 - BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide from the venom of the armed spider Phoneutria nigriventer, produces analgesia by blocking the TRPA1 channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human fetal lung fibroblasts (IMR90) or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), human TRPV1 (hTRPV1-HEK293) or human TRPV4 channels (hTRPV4-HEK293), were used for calcium imaging and electrophysiology. Nociceptive responses induced by TRPA1, TRPV1 or TRPV4 agonists or by bortezomib were investigated in mice. KEY RESULTS: Phα1β selectively inhibited calcium responses and currents evoked by the TRPA1 agonist, allyl isothiocyanate (AITC), on hTRPA1-HEK293, IMR90 fibroblasts and DRG neurons. Phα1β did not affect calcium responses evoked by selective TRPV1 (capsaicin) or TRPV4 (GSK 1016790A) agonists on the various cell types. Intrathecal (i.t.) and intraplantar (i.pl.) administration of low doses of Phα1β (up to 300 pmol per paw) attenuated acute nociception and mechanical and cold hyperalgesia evoked by AITC (i.t. or i.pl.), without affecting responses produced by capsaicin or hypotonic solution. Notably, Phα1β abated the TRPA1-dependent neuropathic pain-like responses induced by bortezomib. In vitro and in vivo inhibition of TRPA1 by Phα1β was reproduced by a recombinant form of the peptide, CTK 01512-2. CONCLUSIONS AND IMPLICATIONS: Phα1β and CTK 01512-2 selectively target TRPA1, but not other TRP channels. This specific action underlines the potential of Phα1β and CTK 01512-2 for pain treatment. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/27759880/The_peptide_Phα1β_from_spider_venom_acts_as_a_TRPA1_channel_antagonist_with_antinociceptive_effects_in_mice_ L2 - https://doi.org/10.1111/bph.13652 DB - PRIME DP - Unbound Medicine ER -