BLOCKADE OF ACETYLCHOLINE-RELEASE AT THE MOTOR END-PLATE BY A POLYPEPTIDE FROM THE VENOM OF PHONEUTRIA NIGRIVENTER

• Autor(a) principal: Souccar, Caden [UNIFESP]
• Data de Publicação: 1995
• Outros Autores: Goncalo, Maria do Carmo [UNIFESP], Lapa, Antonio José [UNIFESP], Troncone, Lanfranco Ranieri Paolo [UNIFESP], Lebrun, Ivo UNIFESP], Magnoli, Fabio [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.1995.tb15931.x/full; http://repositorio.unifesp.br/handle/11600/43179
• topic: PHONEUTRIA NIGRIVENTER; MOTOR NERVE TERMINAL; EXCITATION SECRETION COUPLING; ACH RELEASE

1 The mechanisms underlying the muscle relaxation effect of a fraction (PF3) isolated from the Phoneutria nigriventer spider venom were assessed on mouse diaphragm and chick biventer cervicis muscle preparations.2 PF3 (0.25-4 mu g ml(-1)) produced a concentration-dependent blockade of the nerve-elicited muscle twitch of the mouse diaphragm (IC50 = 0.8 mu g ml(-1)) without affecting the directly induced muscle twitch. In similar preparations, the crude venom (1-10 mu g ml(-1)) produced muscle contracture and blocked both the direct and indirectly induced muscle twitches.3 In the chick biventer cervicis muscle, PF3 (1-5 mu g ml(-1)) blocked the nerve stimulated muscle twitch (IC50 = 1.26 mu g ml(-1)), but did not alter the postjunctional response to exogenous acetylcholine (ACh, 10 mu M-10 mM).4 PF3 (2-8 mu g ml(-1)) reduced the frequency of miniature endplate potentials (m.e.p.ps) recorded intracellularly from the mouse diaphragm muscle fibres by 58 to 64%, and diminished the amplitude of m.e.p.ps by 20 to 40% of control. The relationship between log m.e.p.p. frequency and log [Ca2+](o) was shifted rightwards in the presence of 4 mu g ml(-1) PF3.5 Raising the frequency of m.e.p.ps with high K+ medium or theophylline (3 mM) did not prevent the toxin-induced depression of spontaneous ACh release.6 The quantal content of e.p.ps (m), determined in cut-diaphragm muscle fibres, was reduced by 53% and 77% of control by 1 and 4 mu g ml(-1) PF3, respectively. At 1 mu g ml(-1) the toxin shifted the relationship between log m and log [Ca2+](o) towards higher values without apparent change of the slope.7 E.p.p. trains elicited at 10 to 50 Hz in the-presence of PF3 (1 mu g ml(-1)) exhibited irregular amplitudes and facilitation related to the frequency of nerve stimulation.8 It is concluded that PF3 blocks neuromuscular transmission by acting prejunctionally and reducing the nerve-evoked transmitter release. The effect was related to a diminished Ca2+ entry into the nerve terminal associated with inhibition of exocytosis.