title: The prejunctional inhibitory effect of suramin on neuromuscular transmission in vitro.
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 microM-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 microM-1 mM) inhibited the motor nerve terminal currents related to Ca2+ influx concentration-dependently, but did not affect Na+ currents. Suramin-induced inhibition of Ca2+ currents was not antagonized by ATP gamma S. Suramin (300 microM) 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.
authors.affiliation: Department of Clinical Pharmacology, Groningen Institute for Drug Studies, University of Groningen, Netherlands. r.h.henning@med.rug.nl
authors.forename: R H
authors.initials: RH
authors.lastname: Henning
authors.forename: E G
authors.initials: EG
authors.lastname: Rowan
authors.forename: M F
authors.initials: MF
authors.lastname: Braga
authors.forename: A
authors.initials: A
authors.lastname: Nelemans
authors.forename: A L
authors.initials: AL
authors.lastname: Harvey
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013498:Suramin / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014403:Tubocurarine / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D003473:Neuromuscular Nondepolarizing Agents; D013498:Suramin; D008274:Magnesium; D000109:Acetylcholine; D002118:Calcium; D014403:Tubocurarine