Suramin inhibits the toxic effects of presynaptic neurotoxins at the mousemotor nerve terminals

Citation
Sy. Lin-shiau et Mj. Lin, Suramin inhibits the toxic effects of presynaptic neurotoxins at the mousemotor nerve terminals, EUR J PHARM, 382(2), 1999, pp. 75-80
Citations number
20
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN journal
00142999 → ACNP
Volume
382
Issue
2
Year of publication
1999
Pages
75 - 80
Database
ISI
SICI code
0014-2999(19991008)382:2<75:SITTEO>2.0.ZU;2-D
Abstract
Clinically available chemical antagonists of snake neurotoxins still await to be identified. In this study, we demonstrate that an anti-trypanosomiasi s agent, suramin, is an effective inhibitor of beta-bungarotoxin isolated f rom the venom of Formosan Krait snake. Following intraperitoneal injection (12 ng/g) of beta-bungarotoxin in mice, the time to paralysis (loss a limb withdrawal reflex, 21.8 +/- 3.4 h, n = 4) was significantly prolonged after intravenous injection (16 mu g/g) of suramin (35.9 +/- 4.0 h, n = 4, P < 0 .05). The mechanism of this inhibitory effect of suramin was analyzed at th e mouse nerve terminals. beta-Bungarotoxin (1 mu g/ml) produces an irrevers ible blocking effect of nerve-evoked muscle contractions of mouse phrenic n erve-diaphragm (blocking time 135 +/- 6 min, n = 6). Pretreatment with sura min (0.3 mM) significantly prolonged the blocking time by three-fold. This selective inhibitory effect of suramin was further confirmed when suramin w as shown to delay the neuromuscular blocking effect of another presynaptic neurotoxin, crotoxin (from American rattlesnake venom), but not that of the postsynaptic neurotoxin, alpha-bungarotoxin. Furthermore, suramin inhibite d beta-bungarotoxin in blocking transmitter release as revealed by prolongi ng the time to abolish the end-plate potential amplitude (with suramin, 391 +/- 8 min; without treatment, 141 +/- 5 min). K+ current was measured in t he mouse triangularis sterni preparation; suramin (0.3 mM) had no significa nt effect on beta-bungarotoxin in inhibiting K+ current (77 +/- 3% of contr ol; with suramin 75 +/- 3% of control, respectively). These findings clearl y show that suramin is an inhibitor of presynaptic neurotoxins, mediated by interrupting the toxins in blocking the releasing mechanism of transmitter at the motor nerve terminals. The implication of these findings is that su ramin and related compounds can become useful agents in management of snake bites. (C) 1999 Elsevier Science B.V. All rights reserved.