New insights on arthropod toxins that potentiate erectile function.

The use of natural substances for the treatment of diseases or injuries is an ancient practice of many cultures. According to folklore, natural aphrodisiacs may help to raise libido and increase desire. The supposed aphrodisiacs mainly include a plethora of preparations of plants, among other substances. However, the real boundary between myth and reality has not been established yet in most cases and such boundaries must be drawn by scientific methods. A growing interest of the scientific community has been focused on animal venoms, especially those from arthropods, i.e. spiders and scorpions, which cause priapism, a prolonged and painful erection. This review highlights the studies that have been performed with venoms and toxins from arthropods known to cause priapism, among other toxic symptoms, pointing out some pharmacological approaches for better understanding this effect. To date, the venom of some spiders, mainly Phoneutria nigriventer, and scorpions, such as the yellow South American scorpion Tityus serrulatus, among others, have been known to cause priapism. Since erectile dysfunction (ED) is a growing health problem in the world, more common in patients with vascular diseases as diabetes and hypertension, the use of animal venoms and toxins as pharmacological tools could not only shed light to the mechanisms involved in erectile function, but also represent a possible model for new drugs to treat ED. Unfortunately, attempts to correlate the structure of those priapism-related toxins were unfruitful. Such difficulties lie firstly on the poor data concerning purified priapism-related toxins, instead of whole venoms and/or semi-purified fractions, and secondly, on the scarce available primary sequences and structural data, mainly from spider toxins. It has been shown that all these toxins modify the sodium (Na(+)) channel activity, mostly slowing down its inactivation current. Improving the knowledge on the tertiary structure of these toxins could provide a key in the search of a new drug for ED treatment.

Isolation and structural characterization of a new fibrin(ogen)olytic metalloproteinase from Bothrops moojeni snake venom.

A proteinase, named BmooMPalpha-I, from the venom of Bothrops moojeni, was purified by DEAE-Sephacel, Sephadex G-75 and heparin-agarose column chromatography. The enzyme was purified to homogeneity as judged by its migration profile in SDS-PAGE stained with coomassie blue, and showed a molecular mass of about 24.5 kDa. Its complete cDNA was obtained by RT-PCR and the 615 bp codified for a mature protein of 205 amino acid residues. The multiple alignment of its deduced amino acid sequence and those of other snake venom metalloproteinases showed a high structural similarly, mainly among class P-IB proteases. The enzyme cleaves the Aalpha-chain of fibrinogen first, followed by the Bbeta-chain, and shows no effects on the gamma-chain. On fibrin, the enzyme hydrolyzed only the beta-chain, leaving the gamma-dimer apparently untouched. It was devoid of phospholipase A(2), hemorrhagic and thrombin-like activities. Like many venom enzymes, it is stable at pH values between 4 and 10 and stable at 70 degrees C for 15 min. The inhibitory effects of EDTA on the fibrinogenolytic activity suggest that BmooMPalpha-I is a metalloproteinase and inhibition by beta-mercaptoethanol revealed the important role of the disulfide bonds in the stabilization of the native structure. Aprotinin and benzamidine, specific serine proteinase inhibitors, had no effect on BmooMPalpha-I activity. Since the BmooMPalpha-I enzyme was found to cause defibrinogenation when administered i.p. on mice, it is expected that it may be of medical interest as a therapeutic agent in the treatment and prevention of arterial thrombosis.