Toxicon : official journal of the International Society on Toxinology
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In the four decades since toxinologists in Australia and elsewhere started to investigate the active constituents of venomous cone snails, a wealth of information has emerged on the various classes of peptides and proteins that make their venoms such potent bioactive cocktails. This article provides an overview of the current state of knowledge of these venom constituents, several of which are of interest as potential human therapeutics as a consequence of their high potency and exquisite target specificity. With the promise of as many as 50,000 venom components across the entire Conus genus, many more interesting peptides can be anticipated.
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Biography Historical Article
Struan Sutherland--Doyen of envenomation in Australia.
Struan Sutherland (1936-2002) was the doyen of medical research in the field of envenomation and the ultimate authority on the medical management of envenomated victims in Australia for almost 3 decades. In 1981 as Head of Immunology Research of Commonwealth Serum Laboratories (CSL), he produced an antivenom against the Sydney Funnel-web Spider (Atrax robustus)-an accomplishment that had defied numerous previous attempts. Struan also invented the pressure-immobilisation technique of first-aid for snake bite. ⋯ Struan served the medical fraternity and the public selflessly. He was always available to doctors, or to anybody, to give advice at any hour of the day or night, on management of envenomated victims. Members of the Australian Venom Research Unit, which he founded in 1994 at The University of Melbourne, now continue this 24-h advisory service.
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Bothrops jararaca venom (Bjv) is known to induce local inflammation and severe pain. Since, mast cells are able to secrete mediators involved in algesic processes, in this study we examined the putative role of these cells in the hyperalgesia triggered by Bjv in the rat paw. We noted that treatment with mast cell stabilizer sodium cromoglicate as well as with histamine and 5-hydroxytriptamine receptor antagonists meclizine and methysergide, respectively, inhibited the Bjv-induced hyperalgesia. ⋯ Bjv-induced histamine secretion was clearly sensitive to treatment with sodium cromoglicate and sodium nedocromil. We further observed that metalloproteinase inhibitors 1,10-phenantroline and DM43 inhibited mast cell degranulation in vitro, under conditions where inhibitors of phospholipase A(2) as well as of serine- and cysteine-proteinases were inactive. Altogether, our findings indicate that mast cells seem to contribute to the hyperalgesia caused by Bjv in the rat paw, and also provide evidence that this response might be dependent on the ability of the Bjv to activate directly mast cells.
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Mu-conotoxin SIIIA, a novel blocker of tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels (VGSCs) has been identified from the fish-hunting cone snail, Conus striatus. The deduced sequence consists of a 20-residue signal peptide, a 31-residue pro-peptide, and a 20-residue mature toxin with its N-terminal Gln cyclized and C-terminus amidated. Mu-SIIIA shares the common cysteine arrangement with other mu-conotoxins. ⋯ Similarly, one crucial basic residue (Arg12 in mu-PIIIA) is replaced by serine in the latter two toxins. Such differences might endow them with the capacity to selectively inhibit TTX-S or TTX-R VGSCs. Considering that TTX-R VGSCs predominantly expressed in DRG neurons play pivotal roles in the nociceptive information transmission and that their specific antagonists are still lacking, mu-SIIIA might provide a useful tool for functional studies of these channels, and potentially be developed as an efficient pain killer.
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Comparative Study
Characterization of the acute pancreatitis induced by secretory phospholipases A2 in rats.
Acute pancreatitis (AP) is an inflammatory disease of the pancreas characterized by local inflammation and extrapancreatic effects such as lung injury. Secretory phospholipases A(2) (PLA(2)s) have been implicated in triggering AP, but their exact role to evoke AP is largely unknown. Therefore, we have tested the ability of sPLA(2)s to induce AP in rats, using venom sPLA(2)s with residual or high enzymatic activity (bothropstoxin-II and Naja mocambique mocambique venom PLA(2), respectively), as well as sPLA(2) devoid of catalytic activity (piratoxin-I). ⋯ The lung myeloperoxidase and serum amylase were also increased for all groups, although the Naja mocambique mocambique venom PLA(2) induced higher lung myeloperoxidase and serum amylase values, compared with piratoxin-I and/or bothropstoxin-II. Histopathology of pancreas and lungs in piratoxin-I-injected rats showed interstitial oedema in both tissues, and neutrophil infiltration with acinar cell necrosis in pancreas. In conclusion, sPLA(2)s induce AP in rats and the catalytic activity is not essential to induce the local effects in pancreas, although it appears to contribute partly to the remote lung injury.