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Blockade of acetylcholine release at the motor endplate by a polypeptide from the venom of Phoneutria nigriventer
Author(s) -
Souccar Caden,
Gonçalo Maria do Carmo,
Lapa Antonio José,
Troncone Lanfranco Ranieri Paolo,
Lebrun Ivo,
Magnoli Fabio
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15931.x
Subject(s) - acetylcholine , neuromuscular transmission , neuromuscular junction , chemistry , venom , muscle contraction , medicine , endocrinology , muscle relaxation , curare , neuromuscular blockade , anatomy , pharmacology , anesthesia , biology , biochemistry , neuroscience
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 μg ml −1 ) produced a concentration‐dependent blockade of the nerve‐elicited muscle twitch of the mouse diaphragm (IC 50 =0.8 μg ml −1 ) without affecting the directly induced muscle twitch. In similar preparations, the crude venom (1–10 μg 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 μg ml −1 ) blocked the nerve stimulated muscle twitch (IC 50 =1.26 μg ml −1 ), but did not alter the postjunctional response to exogenous acetylcholine (ACh, 10 μ m ‐10m m ). 4 PF3 (2–8 μg 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 [Ca 2+ ] o was shifted rightwards in the presence of 4 μg ml −1 PF3. 5 Raising the frequency of m.e.p.ps with high K + medium or theophylline (3 m m ) 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 μg ml −1 PF3, respectively. At 1 μg ml −1 the toxin shifted the relationship between log m and log [Ca 2+ ] 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 μg 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 Ca 2+ entry into the nerve terminal associated with inhibition of exocytosis.