Poison Effects

speedreader

Arachnobaron
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I have been writing a paper on spider polyamine toxin effects on the human brain. It's just a summary of existing research but some of the applications are hella cool. For example, there exist spider toxin components that have anti-epileptic, anti-convulsant, anti-ischemic, and anti-sclerotic effects. Pretty impressive if you ask me. Btw, if somebody is interested in my review, I can put it up here.
 

MindUtopia

Arachnoking
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Is that similar to the work that Elizabeth Mule is involved with? I remember reading the articles about it.
 

speedreader

Arachnobaron
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The 10-year old? I don't think she is involved in any research that I know of. My paper is for a neurobiology class at UC Berkeley and is based on research published in mag-s like Nature.
 

Brian F.

Arachnobaron
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I have been writing a paper on spider polyamine toxin effects on the human brain. It's just a summary of existing research but some of the applications are hella cool. For example, there exist spider toxin components that have anti-epileptic, anti-convulsant, anti-ischemic, and anti-sclerotic effects. Pretty impressive if you ask me. Btw, if somebody is interested in my review, I can put it up here.


Yes, please post it.
 

speedreader

Arachnobaron
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Here's the straight copy/paste of my paper. Obviously the format is screwed up and the pic-s are missing, but I don't have the right to post pic-s from those publications here anyway.
Note that the paper assumes significant knowledge of neurobiology, so if you got questions, feel free to ask.



MCB 165, Spring 2007, Professor David Presti





Review
Action of Polyamine Spider Toxins on Mammalian Neuroreceptors and Corresponding Medical Applications
Denis Lankin
Departments of BioEngineering and Statistics, University of California, Berkeley









Abstract

This review summarizes the general facts about polyamine-containing spider toxins, their structure, mechanisms of action, and medical applications. It describes the methods and details of inhibition of mammalian ionotropic channels by the toxins, including various kinds of channel blocks, interactions with other receptor effectors, and selectivity. The features of these drugs and difficulties associated with them are discussed in terms of their potential in scientific, pharmacological, and medical use. The medical applications are elucidated with experimental examples that suggest treatments for serious illnesses such as ischemia, epilepsy and amyotrophic lateral sclerosis.

Keywords: Polyamine toxin; Spider toxin; Ionotropic receptor; Glutamate; AMPA; NMDA; KA; Nicotinic acetylcholine receptor; Channel block; Antagonism; Ischemia; Epilepsy; Amyotrophic lateral sclerosis; Argiope trifasciata; Agelenopsis aperta; Nephila clavata; Parawixia bistriata

Contents
1. Introduction ……………………………………………………………………………….3
2. Polyamine toxin overview ……………………………………………………...............3-7
3. Discussion ………………………………………………………………………………7-9
4. Applications …………………………………………………………………...............9-11
5. Conclusion …………………………………………………………………………...11-12


Introduction


Spider venoms contain a vast variety of biologically active components that exhibit medically interesting effects, including significant neurotransmitter action. It is estimated that the known 39,112 spider species may contain as many as 11 million chemicals (see figure 1a-e) (Estrada et al., 2007). Clearly this plethora of compounds presents a gold mine for pharmacologists and biologists alike, allowing them to pick and choose compounds possessing any given number of parameters, including efficiency, interval of action, delay time, lethal dose, etc. at a given neurotransmitter receptor. Spider toxins include several classes of neurochemcially active compounds, such as polyacylamines, peptides, and more esoteric chemicals. Polyacylamines, generally known as polyamines, represent one of the largest of these classes. They possess a vast variety of specific effects on various ionotropic neuroreceptors and vesicles connected with neurotransmitters. However, polyamine toxins share surprisingly similar structural properties given the diversity of their effects. The discovery, examination, and mechanism deduction of these molecules has been an area of energetic activity among medical scientists and arachnologists alike.


Polyamine toxin overview


Polyamine-containing spider venom components primarily act as blockers of various ionotropic glutamate and nicotinic acetylcholine receptors. For some receptors these antagonists exhibit a simple single-state channel block, but for other receptors, they alternate between open channel and closed channel conformations that transit from one state to another via a complex feedback-oriented mechanism. Most of these mechanisms exhibit complex non-linear voltage-dependence.
Structurally, a polyamine toxin from a spider or a wasp consists of four moieties, the aromatic group at one end (often 2,4-dihydroxyphenyl), connecting asparagine residue, polyamine group, and either guanidine or primary amine on the other end (see figure 2). The large number of primary and secondary amines results in variable valence of these compounds as nitrogen can acquire a net positive charge. This feature seems to play an important role in the open channel block mechanism for this toxin group (Usherwood et al., 2004). Structural similarity between various polyamine compounds from the venoms of different spiders is attributed to the pathway of their biological synthesis, which consists of methodical arrangement of the described groups into the final chemical (Itagaki & Nakajima, 2000).
The mechanism of action of polyamine toxins on N-methyl-D-aspartate (NMDA) receptors is relatively straightforward. A particular subclass of these toxins, argiotoxins from the orb-web spiders Argiope trifasciata (see figure 1a), has been shown to bind to the Mg2+ binding site of the receptor, resulting in strong non-competitive inhibition known as an open channel block. Since the channel transmits Ca2+ ions, the polyvalent properties of polyamines contribute to their effectiveness as non-competitive NMDA receptor antagonists. However, the toxin does compete with other antagonists of NMDA receptor, including MK-801 and Mg2+. Furthermore, high concentration of NMDA in the surroundings prompts the toxin to potentiate currents normally created by NMDA (Usherwood et al., 2004). The potency of the venom depends on the receptor’s subunits due to the difference in an amino acid position, which amino groups of the toxin have to pass for the terminal group to bind to the channel, blocking it. This site is occupied by N in NR2A and NR2B subunits but R in NR3. The latter acid’s basic character precludes the passage of the polyamine groups. Mutation of these positions to Q greatly enhances the potency of the venom (Raditsch et al., 1993).
Polyamine toxins show a similar mechanism of action on α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, where they bind within the open channel, creating an open channel block. The binding greatly depends on high throughput of Ca2+ ions by the receptor, which is achieved through corresponding amino acid sequence of the receptor’s subunits. Therefore, the potency of the toxins is ameliorated by the presence of subunits such GluR2, whose structure prevents channel rectification and, thus, decreases Ca2+ flow. This is due to the difference in one amino acid position, which can be occupied by either Q or R (see figure 3b for alternative binding). If Q is present, the amine groups can pass, allowing the terminal group to bind with G later on in the pore and block the passage (Tikhonov et al., 2002).
The effect of polyamines on Kainate (KA) receptors has not seen much study, primarily due to the receptors’ rapid desensitization as well as the adjacency of AMPA receptors. However, the toxins are presumed to act by an open channel block mechanism that depends on the subunit specification for the same reasons as AMPA mechanism above does (Savidge and Bristow, 1998; Savidge et al., 1999). A site analogous to the Q/R position is also present in KA receptor and has similar effects on potency.
Polyamines exhibit open channel blocking mechanism in inhibition of nicotinic acetylcholine receptors (nAChRs). Some toxins block the receptors located in neurons while others are more potent on muscle receptors (Liu et al., 1997; Mellor et al., 2003; Brier et al., 2003). The circular inside of a nAchR channel is periodically lined with charged amino acids, which allows for Ca2+ selectivity. The shape of these rings varies between muscular and neuronal receptors, contributing to the different toxin effects.
The exact nature of the inhibitory mechanism is uncertain, but it is supposed to be a predominantly open channel block with a variety of alternatives that may transform into each other, including competitive inhibition, closed channel block, and increased desensitization (see figure 3a). The latter is particular interesting since it does not result in complete block of the nAchR channel but rather attenuates its tendency to dilate when exposed to Ca2+. This inhibition is a composite function of voltage that is further complexified by potentiation properties the toxins exhibit (Strømgaard et al., 2005). These observations have lead researchers to believe that there are two binding sites for at least some spider toxins in the nAChRs, as illustrated in figure 3a (Brier et al., 2002, 2003).
Very specific subclasses of polyamine spider venoms exist that exhibit functions, mechanisms, and properties beyond those described above. For example, Agelenopsis aperta is an American funnel web spider that produces several subclasses of such chemicals, collectively known as agatoxins (see figure 1b). While the general effects of α-agatoxins ω-agatoxins are similar to those of the venoms previously described – inhibiting glutamate receptors and generic Ca2+ channels respectively – the other subclass, μ-agatoxins produce the opposite, excitatory, effect on Na+ channels. It is also interesting to note that while ω-agatoxins do inhibit Ca2+ channels, they only produce a partial inhibition of the channel (Venema et al., 1992). Current research suggests that the partial block may be due to reduction of the current in a channel, although the mechanism of this phenomenon is unknown (McDonough et al., 2002). Furthermore, the toxins’ action sites are different from those of the neurotoxins discussed above since ω-agatoxins’ potency does not depend on the structure of the subunits directly. Indeed, they preserve their inhibitory effect regardless of whether Q, R, or even N occupies the analog of the Q/R site. On the other hand, as long as the channel is capable of high throughput of Ca2+, the potency of the venom remains strong (Yan & Adams, 2000). Such specificity allows for interesting further research and designer drugs of high precision.


¬¬Discussion


The fact that polyamine compounds simultaneously antagonize receptors of excitatory neurotransmitters suggests a variety of useful medical applications. While the blockade of nicotinic acetylcholine results in slowdown of sympathetic nervous system, the obstruction of glutamate channels may depress excitatory impulses in the brain during the same time frame. It is important to note that polyamine venom chemicals exhibit significant action not only on the primary glutamate receptor, NMDA, but the secondary ones as well, such as KA and AMPA receptors. However, these neurotoxins preferentially bind to NMDA receptors probably because NR3 subunits, which decrease the venom’s potency, are not as widespread in the brain as GluR2 subunits, which have a similar role in AMPA receptors (Usherwood et al., 2004).
Since the potency of these compounds is very high in natural state, it may be desirable to lessen their effects for chronic applications that do not require immediate strong response. On the other hand, acute over-activity in a patient can probably be ameliorated by application of the natural drug. Regardless, modification of polyamine containing compounds’ potency is fairly straightforward and can be achieved by decreasing the length of the polyamine moiety as well as interchanging the aromatic groups. Interestingly enough, variation of different parts of the toxins results in inconsistent changes in potency across various areas of the brain, such as hippocampus and cortex (Davies et al., 1992; Mueller et al.,1991). Furthermore, the potency of different toxins on different receptors with different subunits varies as well.
These features present an opportunity to design the drugs that would significantly affect only the desired receptors in the appropriate portions of the human brain. It must be noted, however, that since polyamine venoms primarily act via an open channel block, the channel has to be in fact open for the neurotoxin to take effect. This in turn requires a significant presence of the receptor or its agonists and possibly its essential co-agonists. Additionally, one may question the effectiveness of polyamine containing drugs due to their multiple positive charges since this attribute would normally prevent them from crossing the blood brain barrier. Despite this observation, scientific literature suggests that adding polyamines to compounds that normally do not cross the barrier, such as insulin and albumin, will in fact drastically improve their permeability. The exact process involved in this transaction is uncertain, but it is suggested that the polyamine transporter assists in transportation of these molecules (Poduslo & Curran, 1996).
Unfortunately, the use of polyamine compounds is stifled by the relative difficulty of their obtainment, separation and subsequent study. The process of “milking” spider’s fangs for venom is not straightforward (see figure 4) and the amount of venom received through this process is tiny. Moreover, the structural determination of these chemicals is non-trivial, exacerbating partition and identification of these compounds. However, recent developments in Mass Spectrometry allow relatively stream-lined elucidation of the venom’s components’ structures. Furthermore, newer developments in synthesis of these compounds permit easier if not assembly-line production of desired polyamine toxins (Strømgaard et al., 2005). In particular, solid-phase synthesis provides a strong alternative to traditional methods due to its favorable properties, including easier purification, group protection, and construction of combinatorial libraries (Strømgaard et al., 2001). In fact this technique has seen a lot of recent development allowing specification of selectivity and potency of the synthesized compounds. Examples include first construction of combinatorial library (Strømgaard et al., 2001a) and reductive acetylation technique combined with Fukuyama animation that permits the construction of asymmetric polyamine groups (Wang et al., 2000; Strømgaard et al., 2001b).


Applications


Let us consider several of proposed applications of spider polyamine containing toxins in medicine. Of particular interest is the antiepileptic effect of the Joro spider toxin (JSTX-3), native to the Nephila clavata species (see figure 1c). It is known for its extremely selective inhibition of glutamate-mediated ion channels, which makes it a useful implement in the neurosciences. It has been shown that induced epileptic seizures are controlled by NMDA receptor activation in the hippocampus (Smolders et al., 1997). An experiment was conducted on a group of rats predisposed to epilepsy. Epileptic seizures were induced in rats through administration of seizure-generating chemicals like pilocarpine. Then the seizures were interrupted, and after some time, rats were anesthetized, their brains excised, sectioned, and analyzed. In particular, hippocampal neurons underwent thorough electrochemical examination. Artificial cerebro-spinal fluid with and without Mg2+ was added to the brain slices in vitro. Since Mg2+ normally obstructs the NMDA channel, its absence results in over-activity of the receptor. However, addition of JSTX-3 immediately stops this activity. Failing to stop NMDA hyper-excitation results in cell death due to overabundance of Ca2+ that flows through the channels. The epileptic over-activity is likely to be also connected with the other Ca2+ channels, namely AMPA and KA receptors. It has been demonstrated that JSTX-3 antagonizes these receptors as well, creating a synergetic anti-convulsant effect (Salamoni et al., 2005).
Interestingly enough, another spider toxin was shown to have anti-convulsant effects in response to administration of chemicals inducing epilepsy. However, this compound, FrPbAII of the social spider Parawixia bistriata, acts by a very different mechanism (see figure 1d). The venom component inhibits reuptake of GABA by affecting its transporters. Thus, FrPbAII prevents the GABAergic blockade that produces epileptic seizures. Experiments on mice in vivo confirm this neurotoxin’s efficacy at providing seizure protection (Liberato et al., 2006). Therefore, spider toxins present a feasible treatment opportunity for the serious medical condition of epilepsy.
Another interesting application of polyamine toxins centers on their protective role in alleviating brain damage caused by ischemia. This condition frequently follows a stroke, resulting in neuronal damage. In this case, spider toxins such as FTX-3,3, isolated from grass spider Agelenopsis aperta, can act as neuron-protective agents (see figure 1b). The toxin binds to several types of voltage sensitive calcium channels, which are believed to be involved in ischemic cell depolarization that ultimately leads to cell death. Synthetic compounds mirroring the effect of FTX-3,3 have been produced. Moreover, other polyamines, such as JSTX-3 mentioned above, neutralize slow excitatory postsynaptic potentials caused by ischemia. If these potentials are not stemmed, they lead to Ca2+ accumulation and, ultimately, cell death. Thus, spider polyamines may provide an effective multi-layer defense for the consequences of stroke. Furthermore, due to their specificity, they are unlikely to cause the side effects exhibited by the medications currently in use (Estrada et al., 2007).
Additionally, JSTX-3’s inhibition of glutamate channels has proven useful in studying the mechanism of allodynia, a type of pain. The toxin selectively blocks AMPA receptors in the spine. The examination of various pain inducing processes on rats, using different channel inhibitors, allowed elucidation of the pain pathways. The subsequent results suggested the respective roles of NMDA, AMPA, and KA receptors with respect to thermal hyperalgesia, oversensitivity to pain, and mechanical allodynia. These experiments allowed distinguishing between central sensitization and hyperalgesia in patients after surgery. Moreover, since JSTX-3 blocks the channel related to pain transmission, it produces an anesthetic effect, that can be harnessed for pharmacological use (Estrada et al., 2007).
Yet another promising application of spider neurotoxins pertains to the treatment of amyotrophic lateral sclerosis (ASL). One of this condition’s negative effects is enhancement of P-channel Ba2+ current by ImmunoglobinG. This increased current leads to cell death and, ultimately, patient’s death from respiratory failure. However, this extremely harmful pathway can be greatly decreased by stemming Ba2+ current with compounds like a polypeptide toxin pFTX from Agelenopsis aperta spider (see figure 1b). The experiments conducted on guinea pig Purkinje cells in vitro confirm that the synthetic analog of pFTX, sFTX, stops inward Ba2+ current in P-channels. Moreover, both versions of FTX toxin block the P-type channel that contributes to overabundance of Ca2+ during ASL, which leads to similar results as magnified Ba2+ current (Llinas et al., 1993).


Conclusion


Thus, polyamine-containing spider toxins form a group of highly selective, specific, and efficient effectors of neuroreceptors. They primarily act as antagonists of ionotropic channels. The plethora of their mechanisms of action and results thereof are tremendous considering the similarity in the polyamines’ structures. These properties make polyamine toxins incredibly useful for study of various receptors, including those in the human brain. Furthermore, their inhibitory action can be employed in medicine through amelioration of such wasteful conditions as ischemia, epilepsy and amyotrophic lateral sclerosis. Moreover, the great variety of arthropods implies that thousands if not millions of such compounds await discovery for the greater good.
 

speedreader

Arachnobaron
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Appendices of my paper - mostly useless :)

Bibliography

Cited works are listed in alphabetic order by main author’s last name.
Seven primary research articles within the alst 10 years are marked with a * before citation.

*Brier, T.J., Mellor, I.R., Tikhonov, D.B., Neagoe, I., Shao, Z., Brierley, M.J., Strømgaard, K., Jaroszewski, J.W., Krogsgaard-Larsen, P., Usherwood, P.N.R. (2003) Contrasting actions of philanthotoxin-343 and philanthotoxin-(12) on human Muscle Nicotinic Acetylcholine Receptors. Molecular pharmacology 64(4), 954-964.

Brier, T.J., Mellor, I.R., Usherwood (2002) Allosteric and steric interactions of polyamines and polyamine-containing toxins with nicotinic acetylcholine receptors, in: Menez, A.(Ed.), Perspectives in Molecular Toxinology. Wiley, Chichester, pp. 281–296.

Davies, M.S., Baganoff, M.P., Grishin, E.V., Lanthorn, T.H., Volkova, T.M., Watson, G.B., Wiegand, R.C. (1992) Polyamine spider toxins are potent un-competitive antagonists of rat cortex excitatory amino acid receptors. Molecular Pharmacology 227, 51–56.

Estrada, G., Villegas, E., Corzo, G. (2007) Spider Venoms: a rich source of acylpolyamines and peptides as new leads for CNS drugs. Natural Product Reports 24, 145-161.

Itagaki, Y., Nakajima, T. (2000) Acylpolyamines: mass spectrometric analytical methods for Araneidae spider acylpolyamines. Toxin Reviews 19, 23-52.

*Liberato, J.L., Cunha, A.O., Mortari, M.R., Gelfuso, E.A., Beleboni Rde, O., Coutinho-Netto, J., dos Santos, W.F. (2006) Anticonvulsant and anxiolytic activity of FrPbAII, a novel GABA uptake inhibitor isolated from the venom of the social spider Parawixia bistriata (Araneidae: Araneae). Brain research 1124(1):19-27.

Liu, M., Nakazawa, K., Inoue, K., Ohno, Y. (1997) Potent and voltage-dependent block by philanthotoxin-343 of neuronal nicotinic receptor/channels in PC12 cells. British Journal of Pharmacololgy 122, 379–385.

Llinas, R., Sugimori, M., Cherksey, B.D., Smith, R.G., Delbono, O., Stefani, E., Appel, S. (1993) IgG from amyotrophic lateral sclerosis patients increases current through P-type calcium channels in mammalian cerebellar Purkinje cells and in isolated channel protein in lipid bilayer. Proceedings of the National Academy of Sciences of the United States of America 90(24): 11743–11747.

*McDonough, S.I., Boland, L.M., Mintz, I.M., Bean, B.P. (2002) Interactions among toxins that inhibit N-type and P-type calcium channels. The Journal of General Physiology 119 (4), 313–328.


*Mellor, I.R., Brier, T.J., Pluteanu, F., Strømgaard, K., Saghyan, A., Eldursi, N., Brierley, M.J., Andersen, K., Jaroszewski, J.W., Krogsgaard-Larsen, P., Usherwood, P.N.R. (2003) Modification of the philanthotoxin-343 polyamine moiety results in different structure–activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors. Neuropharmacology 44, 70–80.

Mueller, A.L., Albensi, B.C., Ganong, A.H., Reynolds, L.S., Jackson, H. (1991) Arylamine spider toxins antagonize NMDA receptor-mediated synaptic transmission in rat hippocampal slices. Synapse 9, 244–250.

Poduslo, J.F., Curran, G.L. (1996) Polyamine Modification Increases the Permeability of Proteins at the Blood-Nerve and Blood-Brain Barriers. Journal of Neurochemistry 66 (4), 1599–1609.

Raditsch, M., Ruppersberg, J.P., Kuner, T., Gu¨nther, W., Schoepfer, R., Seeburg, P.H., Jahn, W., Witzemann, V. (1993) Subunitspecific block of cloned NMDA receptors by argiotoxin636. FEBS Letters 324, 63–66.

*Salamoni, S.D., Costa da Costa, .J, Palma, M.S., Konno, K., Nihei, K., Tavares, A.A., de Abreu, D.S., Venturin, G.T., de Borba Cunha, F., de Oliveira, R.M., Breda, R.V. (2005) Antiepileptic effect of acylpolyaminetoxin JSTX-3 on rat hippocampal CA1 neurons in vitro. Brain research 1048(1-2),170-6.

*Savidge, J.R., Bristow, D.R. (1998) Ca2+ permeability and Joro spider toxin sensitivity of AMPA and kainite receptors on cerebellar granule cells. European Journal of Pharmacology 351, 131–138.

*Savidge, J.R., Sturgess, N.C., Bristow, D.R., Lock, E.A. (1999) Characterisation of kainate receptor mediated whole-cell currents in rat cultured cerebellar granule cells. Neuropharmacology 38, 375–382.

Smolders, I., Khan, G.M., Manil, J., Ebinger, G., Michotte, Y. (1997) NMDA receptor-mediated pilocarpine-induced seizures: characterization in freely moving rats by microdialysis. British Journal of Pharmacology 121 1171– 1179.

Strømgaard, K., Jensen, L.S., Vogensen, S.B. (2005) Polyamine toxins: development of selective ligands for ionotropic receptors. Toxicon 45, 249-254.

Strømgaard, K., Andersen, K., Krogsgaard-Larsen, P., Jaroszewski, J.W. (2001) Recent advances in the medicinal chemistry of polyamine toxins. Mini Reviews in Medicinal Chemistry 1, 317-338.

Tikhonov, D.B., Mellor, J.R., Usherwood, P.N.R., Magazanik, L.G. (2002) Modeling of the pore domain of the GLUR1 channel: homology with Kþ channel and binding of channel blockers. Biophysical Journal 82, 1884–1893.

Usherwood , Mellor, I.R., Peter N.R. (2004) Targeting ionotropic receptors with polyamine-containing toxins. Toxicon 43, 493-508.

Venema, V.J., Swiderek, K.M., Lee, T.D., Hathaway, G.M., Adams, M.E. (1992) Antagonism of synaptosomal calcium channels by subtypes of v-agatoxins. The Journal of Biological Chemistry 267 (4), 2610–2615.

Yan, L., Adams, M.E. (2000) The spider toxin v-Aga IIIA defines a high affinity site on neuronal high voltage-activated calcium channels. The Journal of Biological Chemistry 275 (28), 21309–21316.

Bibliography of figures

Figure1a-e:

Dope on the Slope: Weekly Invertebrate Blogging (2005) Five of A Kind.
Retrieved April 24, 2007 from
http://meanderthal.typepad.com/dope/2005/10/weekly_inverteb_3.html

San Diego Natural History Museum (2007).
Retrieved April 24, 2007 from
http://www.sdnhm.org/fieldguide/inverts/agel-ape.html

Neighboring Nature (2007) Nephila clavata (Tetragnathidae).
Retrieved April 24, 2007 from
http://www.cyberoz.net/city/sekine/zukax301.htm

Katholieke Universiteit Leuven: Laboratory of Entomology (2006). Photo gallery.
Retrieved April 24, 2007 from
http://bio.kuleuven.be/ento/photo_gallery.htm

Poecilotheria (2005). Erfahrungsberichte.
Retrieved April 24, 2007 from
http://www.poecilotheria.com/berichtepoecilotheria_metallica_male.htm

Figures 2 and 3:

Strømgaard, K., Jensen, L.S., Vogensen, S.B. (2005) Polyamine toxins: development of selective ligands for ionotropic receptors. Toxicon 45, 249-254.

Figure 4:

Estrada, G., Villegas, E., Corzo, G. (2007) Spider Venoms: a rich source of acylpolyamines and peptides as new leads for CNS drugs. Natural Product Reports 24, 145-161.

Figures

Original captions were kept on original figures where appropriate. Figure sources are indicated in bibliography.




Fig.1. Variety of spider species whose venoms are featured in this review. (a) Argiope trifasciata (b) Agelenopsis aperta (c) Nephila clavata (d) Parawixia bistriata and (e) Poecilotheria metallica. Note that the last spider does not directly feature in this review, but presents an excellent example of species variety with its Berkeley colors.





Fig.2. Structure of a typical polyamine containing toxin, PhTX-343.










Fig. 3. Suggested mode of binding of polyamine toxin analogues. (a) Inhibition of nACh receptors by PhTX-12 (5), suggesting that PhTX-12 (5) binds to a site in the channel vestibule of the receptor, thereby enhancing desensitization. (b) Voltage-dependent inhibition of AMPA receptors by PhTX-56 (7), suggesting that the protonated primary amino group of PhTX-56 (7) interacts with Gly18 deep in the ion-channel, well beyond the Q/R-site (Gln-16).



Fig. 4. The venom milking process. (a) Brachypelma vagans is anesthetized with carbon dioxide, (b) electrical stimulation to the chelicera of B. vagans, (c) crude venom from B. vagans. To milk venom from a spider, the fangs of lightly anaesthetized spiders are inserted into thick, soft vinyl tubing, and a low voltage/current electrical shock is applied.
 

Tarantula-Kid

Arachnosquire
Old Timer
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Aug 7, 2003
Messages
65
What about gsmtx-4?

I just became aware of this article because I have been involved in other things lately. I read your article and found it very fascinating. I am very interested in the medical uses of venom and have been since I first learned about the work that Professor Sachs is doing at SUNY. I was surprised this his extensive work on the peptide gsmtx-4 was not mentioned. Are you familiar with this work? GSMTX-4 is a peptide, which like the ones you mentioned, acts a calcium channel blocker. This peptide can stop atrial and ventrical fibrulation in the heart and may be the cure for Duchene's Muscular Dystrophy. If you are not aware of this work, I suggest you contact Professor Sachs to learn more. His website is

http://www.sachslab.buffalo.edu/

I hope this helps! I really would like to hear more about your work since this is what I hope to do after college.

Elizabeth

P.S. BTW, I'm 13, not 10 :)
 

speedreader

Arachnobaron
Old Timer
Joined
May 14, 2005
Messages
330
Oh sorry, when your name got mentioned, I just looked in google... Not the most reliable source of information.
Anyway, I am not actually doing this sort of research for a living, as I am involved in a PhD program in statistics as of now... However, at the time when I was writing this paper, I did quite a lot of reading on the subject matter. Unfortunately, I have never come across Professor Sachs's research - none of the papers I read appeared to refer to his publications and his work was not included in the various searches I was making. Judging from the Professor's website, he lists only one relevant publication on this peptide in a main scientific journal, so that must be why it didn't catch my eye.
Finally, I wrote this paper mostly just for the fun of it. It's certainly not the most scientific or unbiased of articles and a lot of interesting research is bound to be out of its scope.
 

Tarantula-Kid

Arachnosquire
Old Timer
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Messages
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I have some of Professor Sachs articles. If you are interested, send me a PM with an email address to send them to. His website has not been updated in a while, obviously by the cover.
 

speedreader

Arachnobaron
Old Timer
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Messages
330
Honestly, I am incredibly busy with my PhD etc... My "to read" list goes on for eternity. But if I ever feel like reading up on toxins again, I'll give you a pm.
 
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