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Toxins 2018, 10(1), 12; https://doi.org/10.3390/toxins10010012

Peripheral 5-HT3 Receptors Are Involved in the Antinociceptive Effect of Bunodosine 391

1
Laboratory of Pain and Signaling, Butantan Institute, Av. Vital Brasil, 1500, 05503-900 São Paulo, SP, Brazil
2
Laboratory of Genetics, Butantan Institute; Av. Vital Brasil, 1500, 05503-900 São Paulo, SP, Brazil
3
Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan
4
Department of Physiology, Bioscience Institute, University of Sao Paulo, Rua do Matão, trav. 14, 321, 05508-090 São Paulo, SP, Brazil
*
Author to whom correspondence should be addressed.
Received: 27 October 2017 / Revised: 6 December 2017 / Accepted: 20 December 2017 / Published: 27 December 2017
(This article belongs to the Special Issue Animal Venoms and Pain)
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Abstract

Bunodosine 391 (BDS 391), a low molecular weight compound isolated from the sea anemone Bunodosoma cangicum, increases the nociceptive threshold and inhibits inflammatory hyperalgesia. Serotonin receptors are involved in those effects. In this study, we have expanded the characterization of the antinociceptive effect of BDS 391 demonstrating that, in rats: (a) the compound inhibits (1.2–12 ng/paw) overt pain, in the formalin test, and mechanical hyperalgesia (0.6–6.0 ng/paw) detected in a model of neuropathic pain; (b) intraplantar administration of ondansetron, a selective 5-HT3 receptor antagonist, blocks the effect of BDS 391, whereas ketanserin, a 5-HT2 receptor antagonist, partially reversed this effect, indicating the involvement of peripheral 5-HT2 and 5-HT3 receptors in BDS 391 antinociception; and (c) in binding assay studies, BDS 391 was not able to displace the selective 5-HT receptor antagonists, suggesting that this compound does not directly bind to these receptors. The effect of biguanide, a selective 5-HT3 receptor agonist, was also evaluated. The agonist inhibited the formalin’s nociceptive response, supporting an antinociceptive role for 5-HT3 receptors. Our study is the first one to show that a non-peptidic low molecular weight compound obtained from a sea anemone is able to induce antinociception and that activation of peripheral 5-HT3 receptors contributes to this effect. View Full-Text
Keywords: BDS 391; sea anemone; antinociception; peripheral 5-HT3 receptors; overt pain; neuropathic pain; inflammatory hyperalgesia BDS 391; sea anemone; antinociception; peripheral 5-HT3 receptors; overt pain; neuropathic pain; inflammatory hyperalgesia
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Ferreira Junior, W.A.; Zaharenko, A.J.; Kazuma, K.; Picolo, G.; Gutierrez, V.P.; de Freitas, J.C.; Konno, K.; Cury, Y. Peripheral 5-HT3 Receptors Are Involved in the Antinociceptive Effect of Bunodosine 391. Toxins 2018, 10, 12.

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