Effects of Spider Venom Toxin PWTX-I (6-Hydroxytrypargine) on the Central Nervous System of Rats

Abstract

The 6-hydroxytrypargine (6-HT) is an alkaloidal toxin of the group of tetrahydro-β-carbolines (THβC) isolated from the venom of the colonial spider Parawixia bistriata. These alkaloids are reversible inhibitors of the monoamine-oxidase enzyme (MAO), with hallucinogenic, tremorigenic and anxiolytic properties. The toxin 6-HT was the first THβC chemically reported in the venom of spiders; however, it was not functionally well characterized up to now. The action of 6-HT was investigated by intracerebroventricular (i.c.v.) and intravenous (i.v.) applications of the toxin in adult male Wistar rats, followed by the monitoring of the expression of fos-protein, combined with the use of double labeling immunehistochemistry protocols for the detection of some nervous receptors and enzymes related to the metabolism of neurotransmitters in the central nervous system (CNS). We also investigated the epileptiform activity in presence of this toxin. The assays were carried out in normal hippocampal neurons and also in a model of chronic epilepsy obtained by the use of neurons incubated in free-magnesium artificial cerebro-spinal fluid (ACSF). Trypargine, a well known THβC toxin, was used as standard compound for comparative purposes. Fos-immunoreactive cells (fos-ir) were observed in hypothalamic and thalamic areas, while the double-labeling identified nervous receptors of the sub-types rGlu2/3 and NMR1, and orexinergic neurons. The 6-HT was administrated by perfusion and ejection in “brain slices” of hippocampus, inducing epileptic activity after its administration; the toxin was not able to block the epileptogenic crisis observed in the chronic model of the epilepsy, suggesting that 6-HT did not block the overactive GluRs responsible for this epileptic activity.

Recent progress in neuroactive marine natural products

“…The trypargine derivatives ( 191–192 ) are bioactive β-carboline alkaloids found from an African frog, 245 venom of the Brazilian colonial spider, 246 a marine tunicate, 247 and a marine sponge. 248 The marine-derived 193 and its analogues were synthesized as β-carboline alkaloids are known to exhibit variety of biological activity, and the structure of 193 overlaps to some degree with the H3 pharmacophore (Scheme 10).…”

Peptidomic Analysis of Animal Venoms

“…Therefore, the components of animal venoms are important biological tools for studying these receptors, and the discovery of molecules in venoms with selective activity for these receptors represents a very attractive approach to the search for new drugs. The venom components may therefore be probed for the development of new therapies for pain management [31], new anti-arrhythmic [32], anticonvulsant [33] or anxiolytic drugs [34], new antimicrobial agents [35][36][37] or pesticides [38,39], etc. Even a substance that causes priapism has been isolated from the venom of a Brazilian spider [40], becoming a potential drug candidate to attend erectile dysfunction.…”