OBJECTIVES: To investigate the capacity of voltage-gated Na(+) channel activators such as batrachotoxin, aconitine, veratridine, Ts1 (formerly Tityus gamma-toxin), and brevetoxin-3 to induce relaxation of rabbit isolated corpus cavernosum (RbCC) and the pharmacologic mechanisms underlying this phenomenon. The voltage-gated Na(+) channels of the corpus cavernosum are essential for erectile function. A number of biologic toxins exert their effects by modifying the properties of these channels. METHODS: Male New Zealand white rabbits were anesthetized with pentobarbital sodium. Strips of RbCC were transferred to 10-mL organ baths containing oxygenated and warmed Krebs solution. The RbCC strips were connected to force-displacement transducers, and changes in isometric force were recorded using a PowerLab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 micromol/L). RESULTS: The binding site-2 (batrachotoxin, aconitine, and veratridine) and binding site-5 (brevetoxin-3) voltage-gated Na(+) channel activators caused slow-onset RbCC relaxations, and the binding site-4 activator Ts1 produced transitory relaxations followed by a return to baseline. The Na(+)channel blockers tetrodotoxin and saxitoxin (0.1 micromol/L each) abolished the relaxations induced by these agonists. Similarly, the nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester (100 micromol/L) markedly reduced the relaxations and l-arginine (1 mmol/L) restored the relaxations. The soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxidiazolo[4,3-alpha] quinoxalin-1-one (10 micromol/L) reduced the relaxations, and the phosphodiesterase type 5 inhibitor sildenafil (100 nmol/L) significantly potentiated the relaxations by all activators. CONCLUSIONS: Our results indicate that the relaxations evoked by selective activators of voltage-gated Na(+) channels are mediated by the release of nitric oxide from nitrergic nerves and the activation of the nitric oxide-cyclic guanosine monophosphate pathway in the smooth muscle cells of erectile tissue.
OBJECTIVES: To investigate the capacity of voltage-gated Na(+) channel activators such as batrachotoxin, aconitine, veratridine, Ts1 (formerly Tityus gamma-toxin), and brevetoxin-3 to induce relaxation of rabbit isolated corpus cavernosum (RbCC) and the pharmacologic mechanisms underlying this phenomenon. The voltage-gated Na(+) channels of the corpus cavernosum are essential for erectile function. A number of biologic toxins exert their effects by modifying the properties of these channels. METHODS: Male New Zealand white rabbits were anesthetized with pentobarbital sodium. Strips of RbCC were transferred to 10-mL organ baths containing oxygenated and warmed Krebs solution. The RbCC strips were connected to force-displacement transducers, and changes in isometric force were recorded using a PowerLab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 micromol/L). RESULTS: The binding site-2 (batrachotoxin, aconitine, and veratridine) and binding site-5 (brevetoxin-3) voltage-gated Na(+) channel activators caused slow-onset RbCC relaxations, and the binding site-4 activator Ts1 produced transitory relaxations followed by a return to baseline. The Na(+)channel blockers tetrodotoxin and saxitoxin (0.1 micromol/L each) abolished the relaxations induced by these agonists. Similarly, the nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester (100 micromol/L) markedly reduced the relaxations and l-arginine (1 mmol/L) restored the relaxations. The soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxidiazolo[4,3-alpha] quinoxalin-1-one (10 micromol/L) reduced the relaxations, and the phosphodiesterase type 5 inhibitor sildenafil (100 nmol/L) significantly potentiated the relaxations by all activators. CONCLUSIONS: Our results indicate that the relaxations evoked by selective activators of voltage-gated Na(+) channels are mediated by the release of nitric oxide from nitrergic nerves and the activation of the nitric oxide-cyclic guanosine monophosphate pathway in the smooth muscle cells of erectile tissue.
Authors: Kenia P Nunes; Marta N Cordeiro; Michael Richardson; Marcia N Borges; Simone O F Diniz; Valbert N Cardoso; Rita Tostes; Maria Elena De Lima; Robert Clinton Webb; Romulo Leite Journal: J Sex Med Date: 2010-08-16 Impact factor: 3.802
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Authors: Rafael Campos; Fabíola Z Mónica; Renata Lopes Rodrigues; Julio Alejandro Rojas-Moscoso; Ronilson Agnaldo Moreno; José Carlos Cogo; Marco Antonio de Oliveira; Edson Antunes; Gilberto De Nucci Journal: PLoS One Date: 2017-08-24 Impact factor: 3.240
Authors: José Britto-Júnior; Felipe Fernandes Jacintho; Rafael Campos; David Halen Araújo Pinheiro; Guilherme M Figueiredo Murari; Valéria B de Souza; André A Schenka; Fabíola Z Mónica; Ronilson Agnaldo Moreno; Edson Antunes; Gilberto De Nucci Journal: Biol Open Date: 2021-01-20 Impact factor: 2.643