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The prejunctional inhibitory effect of suramin on neuromuscular transmission in vitro

Henning, R.H. and Rowan, E.G. and Braga, M.F.M. and Nelemans, A. and Harvey, A.L. (1996) The prejunctional inhibitory effect of suramin on neuromuscular transmission in vitro. European Journal of Pharmacology, 301 (1-3). pp. 91-97. ISSN 0014-2999

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Abstract

The P2 purinoceptor antagonist suramin reverses skeletal muscle paralysis evoked by non-depolarizing neuromuscular blocking agents in vitro and in vivo. To further study the action of suramin on neuromuscular transmission, (miniature) endplate potentials ((m.)e.p.ps), motor nerve terminal currents and the release of radiolabeled acetylcholine was measured in isolated nerve-muscle preparations. In preparations paralysed by low Ca2+/high Mg2+ conditions, suramin (10 μM-1 mM) induced a concentration-dependent decrease in quantal content of the e.p.ps without affecting m.e.p.ps. Suramin reversed neuromuscular block by d-tubocurarine in these preparations. In erabutoxin paralysed preparations, suramin (40 μM-1 mM) inhibited the motornerve terminal currents related to Ca2+ influx concentration-dependently, but did not affect Na+ currents. Suramin-induced inhibition of Ca2+ currents was not antagonized by ATPγS. Suramin (300 μM) reduced [14C]acetylcholine outflow in non-paralysed rat phrenic nerve-hemidiaphragm preparations by 32%. As suramin did not chelate Ca2+, these results indicate that suramin inhibits neuromuscular transmission by blocking prejunctional Ca2+ channels, thereby decreasing acetylcholine release upon nerve stimulation.