Antinociceptive effect of Lonchocarpus araripensis lectin: activation of l -arginine/NO/cGMP/K + ATP signaling pathway
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Inflammopharmacology
ORIGINAL ARTICLE
Antinociceptive effect of Lonchocarpus araripensis lectin: activation of l‑arginine/NO/cGMP/K+ATP signaling pathway Ana Maria S. Assreuy1 · Renata Morais Ferreira Amorim1 · Stephanie Lian Martins1 · Maria Gleiciane de Queiroz Martins2 · João Batista Cajazeiras2 · Mayara Torquato Lima da Silva3 · Alana Freitas Pires4 · Kyria Santiago Nascimento5 · Benildo Sousa Cavada5 · Mário Rogério Lima Mota6 Received: 4 March 2020 / Accepted: 4 June 2020 © Springer Nature Switzerland AG 2020
Abstract Objective and design The involvement of nitric oxide pathway in the antinociceptive activity of Lonchocarpus araripensis lectin (LAL) was investigated in the model of carragenan-induced hypernociception. Methods Swiss mice received LAL (0.01–10 mg/kg; i.v.) 30 min before s.c. injection of carragenan in the paws. For the involvement of nociceptive pathways, animals were previously treated with the blockers: NOS (L-NAME, aminoguanidine, 7-nitroindazole); soluble guanylyl cyclase (ODQ); channels of ATP-dependent K + (glibenclamide); L-type C a2+ (nifedipine), 2+ − or Ca -dependent Cl (niflumic acid). Participation of lectin domain was evaluated by injection of LAL associated with N-acetyl-glucosamine (GlcNAc). nNOS gene relative expression was evaluated in the paw tissues and nNOS immunostaining in dorsal root ganglia. Results LAL at all doses inhibited carrageenan-induced hypernociception (4.12 ± 0.58 g), being maximal at 10 mg/kg (3 h: 59%), and reversed by GlcNAc. At this time, LAL effect was reversed by nifedipine (39%), niflumic acid (59%), L-NAME (59%), 7-nitroindazole (44%), ODQ (45%), and glibenclamide (34%), but was unaltered by aminoguanidine. LAL increased (95%) nNOS gene expression in mice paw tissues, but not its immunoexpression in the dorsal root ganglia. Conclusion The antinociceptive effect of Lonchocarpus araripensis lectin involves activation of the l-arginine/NO/GMPc/ K+ATP pathway. Keywords Dalbergieae lectin · Hypernociception · nNOS · Nitric oxide
Introduction Nitric oxide (NO) is an important neurotransmitter involved in the nociceptive process that contributes to the development of central sensitization in the dorsal horn of the spinal cord. However, experimental data have demonstrated the * Ana Maria S. Assreuy [email protected] 1
Instituto Superior de Ciências Biomédicas, Universidade Estadual Do Ceará, Av. Dr. Silas Munguba, 1700, Fortaleza, CE 60740‑000, Brazil
Programa de Pós‑Graduação Em Biotecnologia, Centro Universitário INTA (UNINTA), Rua Cel Antônio Rodrigues Magalhães, 359, Sobral, CE 62050‑100, Brazil
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Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis, SC 88040‑900, Brazil
inhibitory role of NO in nociception both in peripheral and central nervous system. In vitro, the endogenous NO produced in cultured neurons of dorsal root ganglia decreases mechanosensitivity via inhibition of voltage-gated Na+ and Ca2+ channels (Chaban et al. 2001). In
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