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4-Aminopyridine inhibits the neuromuscular effects of nitric oxide and 8-Br-cGMP.
Queiroz, R N; Ramos, E R P; Alves-Do-Prado, W.
Afiliação
  • Queiroz RN; Departamento de Medicina, Centro de Ciências da Saúde, Universidade Estadual de Maringá, Maringá, PR, Brasil.
Braz J Med Biol Res ; 36(7): 937-41, 2003 Jul.
Article em En | MEDLINE | ID: mdl-12845382
The effects induced by nitric oxide (NO) in different tissues depend on direct and/or indirect interactions with K+ channels. The indirect interaction of NO is produced by activation of guanylyl cyclase which increases the intracellular cGMP. Since NO, cGMP and 4-aminopyridine alone induce tetanic fade and increase amplitude of muscular contractions in isolated rat neuromuscular preparations, the present study was undertaken to determine whether or not the neuromuscular effects of NO and 8-Br-cGMP can be modified by 4-aminopyridine. Using the phrenic nerve and diaphragm muscle isolated from male Wistar rats (200-250 g), we observed that L-arginine (4.7 mM) and 8-Br-cGMP (18 M), in contrast to D-arginine, induced an increase in the amplitude of muscle contraction (10.5 0.7%, N = 10 and 8.0 0.7%, N = 10) and tetanic fade (15 2.0%, N = 8 and 11.6 1.7%, N = 8) at 0.2 and 50 Hz, respectively. N G-nitro-L-arginine (4 mM, N = 8 and 8 mM, N = 8) antagonized the effects of L-arginine. 4-Aminopyridine (1 and 10 M) caused a dose-dependent increase in the amplitude of muscle contraction (15 1.8%, N = 9 and 40 3.1%, N = 10) and tetanic fade (17.7 3.3%, N = 8 and 37.4 1.3%, N = 8). 4-Aminopyridine (1 M, N = 8) did not cause any change in muscle contraction amplitude or tetanic fade of preparations previously paralyzed with d-tubocurarine or stimulated directly. The effects induced by 4-aminopyridine alone were similar to those observed when the drug was administered in combination with L-arginine or 8-Br-cGMP. The data suggest that the blockage of K+ channels produced by 4-aminopyridine inhibits the neuromuscular effects induced by NO and 8-Br-cGMP. Therefore, the presynaptic effects induced by NO seem to depend on indirect interactions with K+ channels.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nervo Frênico / 4-Aminopiridina / GMP Cíclico / Fatores Relaxantes Dependentes do Endotélio / Contração Muscular / Óxido Nítrico Limite: Animals Idioma: En Revista: Braz J Med Biol Res Ano de publicação: 2003 Tipo de documento: Article País de afiliação: Brasil País de publicação: Brasil
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nervo Frênico / 4-Aminopiridina / GMP Cíclico / Fatores Relaxantes Dependentes do Endotélio / Contração Muscular / Óxido Nítrico Limite: Animals Idioma: En Revista: Braz J Med Biol Res Ano de publicação: 2003 Tipo de documento: Article País de afiliação: Brasil País de publicação: Brasil