The Facilitatory Effect of Casearia sylvestris Sw. (guacatonga) Fractions on the Contractile Activity of Mammalian and Avian Neuromuscular Apparatus

Autor(es):Mostrar menos -

Werner, Adriana C. ^[1] ; Ferraz, Miriele C. ^[1] ; Yoshida, Edson H. ^[1] ; Tribuiani, Natalia ^[1] ; Gautuz, Jean A. A. ^[2] ; Santana, Monique N. ^[2] ; Dezzotti, Bruna A. ^[2] ; de Miranda, Vanessa G. ^[2] ; Foramiglio, Ameris L. ^[2] ; Rostelato-Ferreira, Sandro ^[3] ; Tavares, Renata V. da Silva ^[1] ; Hyslop, Stephen ^[4] ; Oshima-Franco, Yoko ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sorocaba UNISO, Programa Posgrad Ciencias Farmaceut, BR-18023000 Sorocaba, SP - Brazil

^[2] Univ Sorocaba UNISO, Pharm Undergrad Course, BR-18023000 Sorocaba, SP - Brazil

^[3] Paulista Univ UNIP, Pharm Undergrad Course, BR-10087101 Sorocaba, SP - Brazil

^[4] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Dept Pharmacol, BR-13083887 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CURRENT PHARMACEUTICAL BIOTECHNOLOGY; v. 16, n. 5, p. 468-481, 2015.
• Citações Web of Science: 1

Resumo

Many natural products influence neurotransmission and are used clinically. In particular, facilitatory agents can enhance neurotransmission and are potentially useful for treating neuromuscular diseases in which muscular weakness is the major symptom. In this work, we investigated the facilitatory effect of apolar to polar fractions of Casearia sylvestris Sw. (guacatonga) on contractility in mouse phrenic nerve-diaphragm (PND) and chick biventer cervicis (BC) neuromuscular preparations exposed to indirect (via the nerve; 3 V stimuli) and direct (30 V stimuli) muscle stimulation in the absence and presence of pharmacological antagonists. Methanolic and ethyl acetate fractions, but not hexane or dichloromethane fractions, exerted a facilitatory effect on PND (indirect stimulation). The methanolic fraction was chosen for further assays to assess the involvement of: 1) presynaptic sites (axons or nerve terminals), 2) postsynaptic sites (cholinergic receptors, sarcolemma or T-tubules), and 3) the synaptic cleft (acetylcholinesterase enzyme). In preparations treated with d-tubocurarine, the methanolic fraction did not cause facilitation in response to direct stimuli; this fraction was also unable to reverse dantrolene-induced blockade (indirect stimulation). In curarized preparations, the methanolic fraction either restored neuromuscular transmission (mimicking the effect of neostigmine) or failed to cause any recovery of neurotransmission. In the presence of 3,4-diaminopyridine (3,4-DAP), the methanolic fraction decreased twitch amplitude, whereas at a high frequency of stimulation (40 Hz) there was an increase in tetanic tension. In BC preparations, the methanolic fraction did not affect contractures to exogenous acetylcholine or potassium chloride. Incubation with atropine showed there was certain modulation by prejunctional nicotinic receptors, whereas treatment with nifedipine showed that the neurofacilitation required the entry of extracellular calcium. Tetrodotoxin did not prevent the facilitatory effect of 3,4-DAP or neostigmine, but antagonized the response to the methanolic fraction. These findings indicate that neuronal sodium channels have an important role in the facilitatory response to the methanolic fraction, with extracellular calcium entry via calcium channels modulating this neurofacilitation. Possible modulation of prejunctional cholinoceptors was not excluded, particularly in view of certain antagonism by the methanolic fraction at muscarinic receptors. Since facilitation by the methanolic fraction involved enhanced acetylcholine release, use of this fraction could be potentially beneficial in neuromuscular diseases and in the reversal of residual paralysis in the post-operative period or after local anaesthesia. (AU)

• Processo FAPESP: 12/20591-0 - A junção neuromuscular como ferramenta fisiológica ao estudo farmacológico
• Beneficiário: Edson Hideaki Yoshida
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 08/11005-5 - Dipteryx alata Vogel: estudos da ação antiofídica e de toxicidade
• Beneficiário: Yoko Oshima Franco
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 04/09705-8 - Investigacao farmacologica da atividade antipeconhenta de fracoes obtidas de extratos de casearia sylvestris sw.
• Beneficiário: Yoko Oshima Franco
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/50669-6 - RTI - 2008 - Plano de aplicação de recursos - reserva técnica para custos de infra-estrutura institucional para pesquisa
• Beneficiário: Yoko Oshima Franco
• Modalidade de apoio: Auxílio à Pesquisa - Reserva Técnica para Infraestrutura Institucional de Pesquisa
• Processo FAPESP: 12/08271-0 - IDENTIFICAÇÃO E FARMACODINÂMICA DE FRAÇÕES NEUROFACILITADORAS DA Casearia sylvestris SW. NA JUNÇÃO NEUROMUSCULAR
• Beneficiário: Yoko Oshima Franco
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/52643-4 - Estudo da capacidade neutralizante do extrato hidroalcoolico de camellia sinensis (cha verde) contra os efeitos neurotoxico e miotoxico da bothropstoxina-i (bothrops jararacussu).
• Beneficiário: Yoko Oshima Franco
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/53883-6 - Dipteryx alata vogel: estudo da acao antiofidica e da toxicidade.
• Beneficiário: Yoko Oshima Franco
• Modalidade de apoio: Auxílio à Pesquisa - Regular