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

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

Author Souccar, Caden Autor UNIFESP Google Scholar
Goncalo, Maria do Carmo Autor UNIFESP Google Scholar
Lapa, Antonio José Autor UNIFESP Google Scholar
Troncone, Lanfranco Ranieri Paolo Autor UNIFESP Google Scholar
Lebrun, Ivo UNIFESP] Google Scholar
Magnoli, Fabio Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords PHONEUTRIA NIGRIVENTER
MOTOR NERVE TERMINAL
EXCITATION SECRETION COUPLING
ACH RELEASE
Language English
Date 1995-12-01
Published in British Journal Of Pharmacology. Basingstoke: Stockton Press, v. 116, n. 7, p. 2817-2823, 1995.
ISSN 0007-1188 (Sherpa/Romeo, impact factor)
Publisher Stockton Press
Extent 2817-2823
Origin http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.1995.tb15931.x/full
Access rights Open access Open Access
Type Article
Web of Science ID WOS:A1995TG20600005
URI http://repositorio.unifesp.br/11600/43179

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