Suramin inhibits the early effects of PLA 2 neurotoxins at mouse neuromuscular junctions: A twitch tension study

Research Report

J Venom Res (2011), Vol 2, 6-10

Published online: 02 January 2011

Full Text: (PDF ~384kb) | (PubMed Central Record HTML)

Behrooz Fathi †*, Alan L Harvey ‡ and Edward G Rowan ‡

† Department of Pharmacology, School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran

‡ Strathclyde Institute of Pharmacy and Biomedical Sciences , University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom


*Correspondence to: Behrooz Fathi, Email: behrooz840@yahoo.com


Received: 22 December 2010, Accepted: 02 January 2011


© Copyright The Authors


ABSTRACT

Several phospholipase A 2 ( PLA 2) neurotoxins from snake venoms can affect acetylcholine release at the neuromuscular junction. In isolated nerve-muscle preparations three distinct phases have been described for this phenomenon: An initial transient decrease in twitch tension; a second facilitatory phase during which twitch height is greater than control twitch height; and the last phase which causes a reduction in twitch height that finally results in paralysis . Suramin has been reported to inhibit the toxic effects of b -bungarotoxin and another PLA 2 neurotoxin, crotoxin in vitro and in vivo. We have further examined the effects of suramin on the three phases of the effects of the presynaptic PLA 2 neurotoxins b -bungarotoxin, taipoxin and ammodytoxin on mouse phrenic nerve-hemidiaphragm preparations. When preparations were pre-treated with suramin (0.3mM), the early biphasic effects (depression followed by facilitation) were abolished, and the time taken for final blockade induced by b -bungarotoxin, taipoxin and ammodytoxin A was significantly prolonged. In contrast, suramin did not significantly affect the facilitation induced by the potassium channel blocking toxin dendrotoxin I when applied under the same conditions. In addition, application of 0.3mM suramin did not prevent the facilitatory actions of 3,4-diaminopyridine (3,4-DAP) and tetraethylammonium chloride (TEA). Overall, the mechanism whereby suramin reduces the effects of PLA 2 neurotoxins remains elusive. Since suramin reduces both enzyme-dependent and enzyme-independent effects of the toxins, suramin is not acting as a simple enzyme inhibitor. Furthermore, the observation that suramin does not affect actions of standard K + channel blockers suggests that suramin does not stabilise nerve terminals.

KEYWORDS:PLA 2 neurotoxins, b -bungarotoxin, Taipoxin, Ammodytoxin, Suramin, Mouse phrenic nerve hemidiaphragm preparations