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Jaburetox, a natural insecticide derived from Jack Bean Urease, activates voltage-gated sodium channels to modulate insect behavior

dos Santos, Douglas Silva, Zanatta, Ana Paula, Martinelli, Anne Helene Souza, Rosa, Maria Eduarda, de Oliveira, Raquel Soares, Pinto, Paulo Marcos, Peigneur, Steve, Tytgat, Jan, Orchard, Ian, Lange, Angela B., Carlini, Celia R., Dal Belo, Cháriston A.
Pesticide biochemistry and physiology 2019 v.153 pp. 67-76
Canavalia ensiformis, Nauphoeta cinerea, Xenopus laevis, action potentials, antennae, body weight, electric potential, heart rate, insect behavior, insecticides, legs, locusts, mechanism of action, muscles, nerve tissue, oocytes, protocols, sodium, sodium channels, urease
Jaburetox (Jbtx) is an insecticidal peptide derived from Canavalia ensiformis urease, whose mechanism of action is not completely elucidated. We employed behavioral, electromyographical and electrophysiological protocols to identify the cellular and molecular targets involved in the Jbtx entomotoxicity in cockroaches and locusts. In Nauphoeta cinerea, Jbtx (32 μg/g) altered the locomotory behaviour inducing a significative decrease in the distance travelled followed by a significant increase in stopped time (52 ± 85 cm and 2573 ± 89 s, p < .05, n = 40). Jbtx (8 to 32 μg/g body weight, respectively) also increased the leg and antennae grooming activities (p < .05, n = 40, respectively). Jbtx (8 to 16 μg/g) induced a maximum neuromuscular blockade of 80.72% (n = 6, p < .05) and was cardiotoxic, decreasing the cockroach heart rate. The electrophysiological profiles of both muscle and nerve of L. migratoria showed that Jbtx (2.5 × 10−7 and 2.5 × 10−3 μg/ body weight) induced a significant increase in the amplitude of nerve action potentials (n = 5, p < .05). Voltage clamp analysis of Jbtx (200 nM) applied in Xenopus laevis oocytes heterologously expressed with Nav 1.1 channels showed a significant increase in the sodium currents. In conclusion, this work revealed that the entomotoxic activity of Jbtx involves complex behavioral alterations that begins with an initial activation of voltage-gated sodium channels.