Neuroactive Toxins of Spider Venoms

Abstract

A variety of neuroactive toxins have been found in the venom of spiders. The venom of Latrodectus mactans(black widow spider) is known as a potent neurotoxin, fatal to humans and animals. The effective component, α-latrotoxin (Mr=130,000) acts on the nerve terminals, causing massive release of transmitters and depletion of the synaptic vesicles, by inducing influx of cations such as Ca²⁺and Na⁺through the channels existing in the presynaptic nerve terminals.

In the venom of Araneidspiders, a different type of toxin from the black widow spider venom was found. Joro spider toxin (JSTX) from Nephila clavat, NSTX from Nephila maculata, and argiopine (argiotoxin) from Argiope lobataact postsynaptically on glutamate receptors. These toxins share a common structure of a phenolic moiety connected to a polyamine. Chemical synthesis of these low molecular weight toxins has enabled morphological and biochemical studies of the glutamate receptors.

Recently, a third group of neurotoxins was found in genus Agelenidae. A number of toxins isolated from the venom of Agelenopsis aperta, Hololena curtaand Agelena opulentawere found to block synaptic transmission by a presynaptic mechanism. The structures of a number of Agelenidaetoxins have been characterized, and it has been shown that they block presynaptic calcium channels. These toxins should serve as useful tools for isolating and characterizing neuronal calcium channel proteins.     

Spider Polyamine Toxin

In the early 1980s, a new type of polyamine toxins was found in the venom of several orb-web spiders. Joro spider toxins (JSTXs) in the venom of Nephila clavata and Nephila spider toxins (NSTXs) derived from Nephila maculata blocked postsynaptic glutamate receptors in the invertebrate and vertebrate nervous system. Subsequently, chemical characterization and synthesis of JSTXs and NSTXs were carried out. These toxins and a synthetic analog, 1-naphthylacetylated spermine (Naspm), effectively suppressed glutamate channel responses of AMPA/KA type in mammalian central neurons. By use of recombinant subunit receptors expressed in Xenopus oocytes, JSTX was found to cause subunit specific block of the Ca²⁺-permeable AMPA receptors. This specific nature of JSTX was utilized to identify Ca²⁺-permeable AMPA receptors in various neurons and glial cells. The JSTXs strongly suppressed excitatory postsynaptic currents (EPSCs) in the hippocampal CA1 neurons after transient brain ischemia. The results indicate that JSTXs are effective at blocking abnormal EPSCs that may induce Ca²⁺ accumulation leading to delayed neuronal death after transient ischemic insult. Recent evidence shows that Ca²⁺-permeable AMPA receptors are involved in a variety of nervous diseases including amyotrophic lateral sclerosis (ALS) and allodynia. The JSTXs are potentially useful to understand pathogenesis of these diseases.     

Rattlesnake Neurotoxins: Biochemical and Biological Aspects

Abstract

A number of rattlesnake venoms contain potent neurotoxic protein complexes that have phospholipase A₂ activity. Data derived from studies of some of these neurotoxins indicate that neuromuscular transmission is blocked. The primary action appears to be at presynaptic sites, but at high doses interactions with cholinergic receptors reduce postsynaptic responses. The toxin complexes are mixtures of closely related isoforms, each composed of two distinct and separable subunits. The basic protein subunit is a phospholipase which is somewhat toxic whereas the acidic constituent is devoid of toxicity and lacks enzymatic activity. Even though the two subunits have quite different structures, they have considerable sequence similarity, suggesting a common ancestral origin. The acidic subunit enhances the lethal potency of the basic phospholipase component when the two are combined to generate a reconstituted toxin. Evidence suggests the acidic subunit reduces nonspecific binding of the basic phospholipase to membranes, thereby restricting binding of the neurotoxic component to specific sites on toxin sensitive membranes.

This class of toxins has not been used extensively to study subcellular membrane vesicles or cultured cells. Results from some of our studies with isolated rat brain synaptosomes demonstrated that Mojave toxin and the basic subunit isolated from Mojave toxin alter the uptake and release of neurotransmitters. Recent unpublished studies with cultured muscle cells showed marked effects on the fusion process in which primary myoblasts form myotubes. The toxin also reduces the formation of colonies from several clonal myoblast cell lines. The biochemical bases for these observations remain to be determined.     

Peripheral Effects of Tityus serrulatus Scorpion Venom

Abstract

In this review we describe the peripheral effects induced by Tityus serrulatus scorpion venom and two of the most important toxins-tityustoxin and toxin Ts-γ purified from the crude venom. The complex cardiac arrhythmias elicited by the venom or the toxins were explained by the release of catecholamines and acetylcholine. In isolated rat atria, toxin Ts-γ induced mainly cholinergic effects of long duration. Arterial hypertension was mostly due to release of catecholamines from postganglionic nerve endings and adrenal glands with subsequent stimulation of alpha-adrenergic receptors. The pulmonary edema was related to an adrenergic discharge with stimulation of alpha-adrenergic receptors, leading to an increase of preload and afterload and subsequent heart failure (cardiogenic factor) and also release of permeability factors in lungs, such as the platelet-activating factor (non-cardiogenic factor). The complex respiratory arrhythmias elicited by scorpion toxins in rats were mainly due to stimulation of afferent visceral receptors, being therefore reflex in nature. The scorpion toxin (tityustoxin) also induced pre- and postsynaptic actions at the neuromuscular junctions. The purified scorpion toxins evoked, in anesthetized rats, the appearance of acute gastric injuries in the glandular mucosa (ulcers), simultaneously with an increase in volume, acidity and pepsin output of the rat stomach, explained mostly by the release of acetylcholine and histamine.     

Definition of the alpha-KTx15 subfamily

Three novel scorpion toxins, Aa1 from Androctonus australis, BmTX3 from Buthus martensi and AmmTX3 from Androctonus mauretanicus were shown able to selectively block A-type K⁺ currents in cerebellum granular cells or cultured striatum neurons from rat brain. In electrophysiology experiments, the transient A-current completely disappeared when 1 μM of the toxins was applied to the external solution whereas the sustained K⁺ current was unaffected.

The three toxins shared high sequence homologies (more than 94%) and constituted a new ‘short-chain’ scorpion toxin subfamily: -KTx₁₅. Monoiododerivative of ¹²⁵I-sBmTX3 specifically bound to rat brain synaptosomes. Under equilibrium binding conditions, maximum binding was 14 fmol/mg of protein and the dissociation constant (K_d) was 0.21 nM. This K_d value was confirmed by kinetic experiments (k_on=6.0×10⁶ M⁻¹ s⁻¹ and k_off=6.0×10⁻⁴ s⁻¹). Competitions with AmmTX3 and Aa1 with ¹²⁵I-sBmTX3 bound to its receptor on rat brain synaptosomes showed that they fully inhibited the ¹²⁵I-sBmTX3 binding (K_i values of 20 and 44 pM, respectively), demonstrating unambiguously that the three molecules shared the same target in rat brain. A panel of toxins described as specific ligands for different K⁺, Na⁺ and Ca²⁺ channels were not able to displace ¹²⁵I-sBmTX3 from its binding site. Thus, ¹²⁵I-sBmTX3 is a new ligand for a still unidentified target in rat brain. In autoradiography, the distribution of ¹²⁵I-sBmTX3 binding sites in the adult rat brain indicated a high density of ¹²⁵I-sBmTX3 receptors in the striatum, hippocampus, superior colliculus, and cerebellum.     

In vivo [3H]spiperone binding to the rat hippocampal formation: Involvement of dopamine receptors

The existence of DA receptors in the rat hippocampus was demonstrated with an in vivo [³H]spiperone radio-receptor assay. Kinetic studies revealed that maximum binding of [³H]spiperone in hippocampus was much smaller than in striatum and frontal cortex but much higher than in cerebellum. In inhibition studies of [³H]spiperone binding, all neuroleptics tested were active in hippocampus as well as in striatum. In contrast, 5HT antagonists were definetely less potent in these two brain regions than in frontal cortex. Finally, even when 5HT receptors were blocked, dipropyl-ATN and haloperidol remained fully effective in hippocampus, striatum, but also in frontal cortex although to a lesser degree. From these results it was concluded that [³H]spiperone binds mainly to DA receptors in hippocampus as well as in striamtum, whereas both 5HT and DA receptors are present in frontal cortex.     

Autoradiographic mapping of neurotransmitter system receptors in mammalian brain.

Regional localization of neurotransmitter system receptors was visualized in the gerbil grain and in the rat brain using receptor autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyladenosine (CHA), [3H]muscimol, [3H]MK-801, [3H]SCH 23390, [3H]PN200-110, [3H]spiperone, and [3H]naloxone were label muscarinic receptors, adenosine A1 receptors, GABAA receptors, N-methyl-D-aspartate (NMDA) receptors, dopamine D1 receptors, L-type calcium channels, spirodecanone receptors, and opioid receptors, respectively. Regional localization of [3H]QNB, [3H]muscimol, [3H]MK-801, [3H]SCH 23390, and [3H]PN200-110 binding sites in the gerbil brain was relatively similar to that in the rat brain. In contrast, the autoradiographic distribution of [3H]spiperone and [3H]naloxone binding sites in the gerbil was quite different from that in the rat. This phenomenon was found especially in the hippocampus and the cerebellum. The results suggest that the gerbil differs from the rat with respect to spirodecanone and opioid binding sites in the hippocampus and the cerebellum. This finding may help to further elucidate the species differences and relationships for brain function and behavioral pharmacology.     

Cocaine-induced glutamate receptor trafficking is abrogated by extinction training in the rat hippocampus

BackgroundIt has been demonstrated that long-term exposure to cocaine leads to plastic changes in the brain that contribute to the manifestation of addictive behaviors. While attention has mostly focused on the meso-cortico-limbic pathway, the hippocampus seems to play a role in the craving induced by cues in drug addicts, in particular in cue- and drug-induced reinstatement of cocaine seeking. Since glutamate appears to be critical for context-induced drug seeking behaviors, the major aim of our work was to investigate the expression of hippocampal AMPA and NMDA glutamate receptors following repeated cocaine exposure and during extinction training.MethodsWe thus employed the yoked control operant paradigm and exposed the animals to contingent or non-contingent cocaine exposure for 2 weeks and sacrificed the animals after the last self-administration (SA) session and following 1 or 10 days of extinction. Protein levels of glutamate receptors were analyzed by Western blotting.ResultsWe found increased levels of the main subunits of both NMDA and AMPA receptors in the post-synaptic density (PSD) fraction, but not in the whole homogenate, of the hippocampus of animals repeatedly exposed to cocaine indicating increased trafficking toward the membrane of these receptors. Also, we found that extinction abolished such effect, suggesting that the trafficking was tightly linked to the presence of the psychostimulant.ConclusionsThese data reveal a novel, previously unappreciated role of glutamate receptors in the action of cocaine and cocaine-extinction behavior in rat hippocampus.     

Direct autoradiographic localization of adenosine A2 receptors in the rat brain using the A2-selective agonist, [3H]CGS 21680

The regional distribution of adenosine A2 receptors in the rat brain was determined using the A2-selective agonist ligand [3H](2-p-carboxyethyl)phenylamino)-5'-N-carboxamidoadenosine (CGS 21680) by quantitative receptor autoradiography. [3H]CGS 21680 binding was highly localized in the striatal region of the rat brain with the greatest density of binding found in the caudate-putamen, nucleus accumbens and olfactory tubercle. Additionally, lower levels of binding were also found in the globus pallidus. No significant amounts of [3H]CGS 21,680 binding were detected in other brain regions. This localization of brain adenosine A2 receptors was markedly different from the known regional distribution of A1 receptors which are highly concentrated in cerebellum, hippocampus, thalamus and cortex. The present results provide further evidence for a specific contribution of adenosine in the modulation of central neurotransmission.     

Binding of selective antagonists to four muscarinic receptors (M1 to M4) in rat forebrain

To compare the proportions of four muscarinic receptors in different rat brain regions, we used competition curves with four selective antagonists, at 1-[N-methyl-3H]scopolamine methyl chloride [( 3H]NMS) binding equilibrium and after allowing [3H]NMS dissociation for 35 min. Himbacine and methoctramine were shown to discriminate two muscarinic receptor subtypes having a high affinity for 4-diphenylacetoxy-N-methylpiperidine methiodide and hexahydrosiladifenidol, intermediate affinity for pirenzepine, and low affinity for AF-DX 116. One M4 subtype had a high affinity for himbacine and methoctramine; it was found predominantly in homogenates from rat striatum (46% of total [3H]NMS receptors) and in lower proportion in cortex (33% of [3H]NMS receptors) and hippocampus (16% of [3H]NMS receptors). Its binding properties were identical to those of muscarinic receptors in the neuroblastoma x glioma NG 108-15 hybrid, suggesting that it was encoded by m4 mRNA. The M3 subtype (typically found in rat pancreas, a tissue expressing the m3 mRNA) had a low affinity for himbacine and methoctramine and represented about 10% of all [3H]NMS receptors in rat brain cortex, hippocampus, striatum, and cerebellum. M1 and M2 receptors were identified in rat brain by their high affinity for pirenzepine and AF-DX 116, respectively.     

Toxins from Mamba Venoms that Facilitate Neuroiluscular Transmission

Abstract

Venoms from the four species of African mambas have many neurotoxins that are different from other snake neurotoxins. Postjunctional α-neurotoxins, which bind to nicotinic cholinoceptors, appear to be the only type of toxin that mambas have in common with other snakes with neurotoxic venoms. Typical mamba neurotoxins are prejunctional facilitatory toxins and anticholinesterase toxins or fasciculins.

The prejunctional facilitatory toxins enhance the amount of transmitter that is released in response to nerve stimulation. This activity was first demonstrated with dendrotoxin (from Dendroaspis anqusticeps) at the neuromuscular junction, but it can also be observed in both the sympathetic and parasympathetic branches of the autonomic nervous system and in the central nervous system. These facilitatory neurotoxins have 57-60 amino acids in a single polypeptide chain cross-linked by three disulphide bonds. They are structurally homologous to the Kunitz type protease inhibitors such as bovine pancreatic trypsin inhibitor.

The anticholinesterase toxins are specific and powerful in inhibitors (K_i of about 10^?10 M) of acetylcholinesterase from several sources (human erythrocytes, rat brain and muscle, eel electroplax) but they have no effect on acetylcholinesterase from cobra venom or chick brain and muscle. The first two of these inhibitors (from Dendroaspis angusticeps) were called fasciculins because of the long-lasting muscle fasciculations that they produced in mice. Fasciculins have 61 amino acids and four disulphides and show sequence homology with the postjunctional short neurotoxins.

Synergistic interactions between components are characteristic of mamba venoms. One of these components is always a member of the so-called “angusticeps-type” toxins (short neurotoxin homologues of 58-60 amino acids and four disulphides). These toxins are divided into four subgroups, the anticholinesterases constituting subgroup I. Angusticeps-type toxins interact with facilitatory toxins or with so-called “synergistic-type” proteins (toxins of two subunits, each with 62-63 amino acids and joined together by disulphide bonds). The pharmacology of these interactions is not known, only data on the increased lethality of the synergistic mixtures is available.     

Comparison of benzodiazepine receptor binding in membranes from human or rat brain

Specific high affinity binding of [3H]flunitrazepam to membranes from human brain was stimulated by gamma-aminobutyric acid (GABA), pentobarbital, 1-ethyl-4-(isopropylidene-hydrazino)-1H-pyrazolo[3,4b]pyridine-5-carboxy lic acid ethyl ester hydrochloride (SQ 20009) and avermectin B1a and was unaffected by 2 microM 4'-chlorodiazepam (Ro 5-4864) indicating that [3H]flunitrazepam in human brain as well as in rat brain predominantly binds to benzodiazepine receptors specific to brain, which was associated with a GABA receptor and several modulatory binding sites for drugs. The potency of several selective and non-selective ligands for benzodiazepine receptors for inhibition of the binding of [3H]flunitrazepam was compared in membranes from human or rat brain cerebellum, hippocampus and cerebral cortex. It was demonstrated that all these compounds, derived from different chemical structures, had a remarkably similar potency for inhibition of the binding of [3H]flunitrazepam in the corresponding regions of the human or rat brain. However, irreversible labelling of benzodiazepine binding sites with [3H]flunitrazepam and subsequent SDS-polyacrylamide gel electrophoresis and fluorography revealed more photolabelled protein bands in human than in rat cerebellum and hippocampus. The results seem to indicate that, although the pharmacological properties of reversible binding of [3H]flunitrazepam are remarkably similar in membranes from rat or human brain, the molecular heterogeneity of benzodiazepine binding sites is even greater in human than in rat brain.     

Tetanus and botulinum toxins block the release of acetylcholine from slices of rat striatum and from the isolated electric organ of Torpedo at different concentrations

Tetanus toxin, like botulinum toxin type A, blocks cholinergic synaptic transmission at the central and peripheral nervous systems. Nevertheless, the diseases induced by the two toxins are different since tetanus toxin induces a spastic paralysis and botulinum toxin elicits a flaccid paralysis. Thus, we have investigated the sensitivity of a central and a peripheral cholinergic synapse to these two toxins. We have studied the action of both poison on the release of acetylcholine from slices of the rat striatum and from the isolated electric organ of Torpedo, which is homologous to the neuromuscular junction. Acetylcholine release from the rat striatum was continuously monitored by a chemiluminescent method. The secretion of acetylcholine from the electric organ was estimated both by measuring the amplitude of the evoked electrical discharge from stacks of electroplaques, and by continuously monitoring the neurotransmitter release from isolated nerve terminals. Tetanus toxin blocks the electrical discharge of electric organ prisms, and also impairs the release of acetylcholine from the Torpedo electric organ nerve endings. Our results on acetylcholine release show that tetanus toxin is more potent than botulinum toxin type A at the central cholinergic synapse (tetanus/botulinum toxins potency ratio about 100-200) whereas botulinum toxin is the most potent at the peripheral cholinergic synapse (botulinum/tetanus toxins potency ratio about 100).     

mGluR2 positive allosteric modulators: a patent review (2009 – present)

Introduction: The mGlu2 receptor, which belongs to the group II subfamily of metabotropic glutamate receptors (mGlu) along with the mGlu3 receptor, has proven to be of particular importance in neuropharmacology. Preferentially expressed on presynaptic nerve terminals, the mGlu2 receptor negatively modulates glutamate and GABA release and is widely distributed in the brain. High levels of mGlu2 receptors are seen in brain areas such as prefrontal cortex, hippocampus and amygdala where glutamate hyperfunction may be implicated in disorders and diseases such as anxiety and schizophrenia. Given the promise offered by mGlu2/3 receptor activation, there is increased interest in identifying small molecules which activate the receptor. A preferred approach is via positive allosteric modulators (PAMs) which bind at an alternative site to agonists.

Areas covered: This review covers the patent applications which were published between April 2009 and December 2012 on PAMs of the mGlu2, and it is a continuation of an earlier review published in this journal.

Expert opinion: Advances in medicinal chemistry and pharmacology have set the stage in the field of mGlu2 receptor PAMs. Compounds currently advancing in clinical trials will soon establish the therapeutic potential of this allosteric approach.     

Interaction of botulinum type A,B and E derivative toxins with synaptosomes of rat brain

Summary Clostridium botulinum ¹²⁵I-labelled derivative toxin immediately bound to rat synaptosomes. Of the two fragments of type B derivative toxin, the large-molecular-weight fragment (fragment I) inhibited the binding of labelled type B derivative toxin to synaptosomes in the same manner as unlabelled type B toxin did. The inhibition by the small-molecular-weight fragment (fragment II) was less than that by fragment I. These findings suggest that type B toxin binds to synaptosomes mainly with some part of fragment I. The binding of labelled type A and E derivative toxins was inhibited by either of the unlabelled type A or E derivative toxins, but not by type B derivative toxin. It is concluded that synaptosomes of rat brain possess relatively specific binding sites for botulinum toxin types.     

Regional distribution of high affinity binding of 3H-adenosine in rat brain

The high and low affinity adenosine binding sites with Kd values ranging respectively from 0.8 to 1.65 microM and from 3.1 to 13.86 microM were demonstrated in the following rat brain areas: cortex, hippocampus, striatum, cerebellum, diencephalon, and pons-medulla. Adenosine receptors involved in the high affinity binding seem to be mainly Ra-type. The analysis of the regional distribution of 3H-Adenosine showed the highest levels of specific binding in striatum and hippocampus; somewhat smaller values in cortex, cerebellum, and diencephalon, and even lower in pons-medulla.     

3H]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists

R214127 was shown to be a potent and noncompetitive metabotropic glutamate 1 (mGlu1) receptor-selective antagonist. The kinetics and pharmacology of [(3)H]1-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenyl-1-ethanone (R214127) binding to rat mGlu1a receptor Chinese hamster ovary (CHO)-dhfr(-) membranes was investigated, as well as the distribution of [(3)H]R214127 binding in rat brain tissue and sections. Specific binding to rat mGlu1a receptor CHO-dhfr(-) membranes was approximately 92% of total and was optimal at 4 degrees C. Full association was reached within 5 min, and [(3)H]R214127 bound to a single binding site with an apparent K(D) of 0.90 +/- 0.14 nM and a B(max) of 6512 +/- 1501 fmol/mg of protein. Inhibition experiments showed that [(3)H]R214127 binding was completely blocked by 2-quinoxaline-carboxamide-N-adamantan-1-yl (NPS 2390), (3aS,6aS)-6a-naphtalan-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c]furan-1-on (BAY 36-7620), and 7-(hydroxyimino)cyclo-propa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt), but was not displaced by competitive mGlu1 receptor ligands such as glutamate and quisqualate, suggesting that R214127, NPS 2390, BAY 36-7620, and CPCCOEt bind to the same site or mutually exclusive sites. Experiments using rat cortex, striatum, hippocampus and cerebellum revealed that [(3)H]R214127 labeled a single high-affinity binding site (K(D) approximately 1 nM). B(max) values were highest in the cerebellum (4302 +/- 2042 fmol/mg of protein) and were 741 +/- 48, 688 +/- 125, and 471 +/- 68 fmol/mg of protein in the striatum, hippocampus, and cortex, respectively. The distribution of [(3)H]R214127 binding in rat brain was investigated in more detail by radioligand autoradiography. A high density of binding sites was detected in the molecular layer of the cerebellum. Moderate labeling was seen in the CA3 and dentate gyrus of the hippocampus, thalamus, olfactory tubercle, amygdala, and substantia nigra reticulata. The cerebral cortex, caudate putamen, ventral pallidum, and nucleus accumbens showed lower labeling. The high affinity and selectivity of [(3)H]R214127 for mGlu1 receptors renders this compound the ligand of choice to study the native mGlu1 receptor in brain.     

Diphtheria toxin-based targeted toxins that target glioblastoma multiforme

Abstract

Targeted toxins (TTs) are compounds that bind cell surface receptors overexpressed on cancer cells. After the molecule enters the cell, the toxin component migrates to the ribosomes where it blocks protein synthesis killing the cell. Most of these proteins are recombinant and contain a carrier ligand or antibody attached to a modified bacterial toxin such as diphtheria toxin (DT). With respect to cancer, these fusion proteins are active against brain tumor cells that are resistant to chemotherapy and radiation therapy. The toxicity profile for TTs is acceptable and they have been safe in animal studies and demonstrated a therapeutic response in early clinical trials. Those barriers to the successful treatment of brain tumors include poor tumor penetration, immune recognition of DT and the heterogeneity of cancer.     

2-Oxo-2H-Pyrimido[2,1-b]benzothiazoles inhibit brain benzodiazepine receptor binding in vitro

2-Oxo-2H-pyrimido[2,1-b]benzothiazole derivatives were found to inhibit the in vitro binding of (3)H-Ro 15-1788 ((3)H-flumazenil) to rat cortical benzodiazepine receptors with IC(50) values in the range of 0.7-13 micromol/l. The most potent compound, 2-oxo-4-phenyl-2H-pyrimido[2,1-b]- benzothiazole showed a similar potency to inhibit (3)H-Ro 15-1788 binding to membrane preparations of rat brain cortex, cerebellum and hippocampus as well as to various subunit combinations of recombinant human gamma-aminobutyric acid(A)/benzodiazepine receptors. Scatchard plot analysis showed that 2-oxo-4-phenyl-2H-pyrimido[2,1-b]benzothiazole is a competitive inhibitor of (3)H-Ro 15-1788 binding to rat brain cortical membrane preparations.     

Spider Neurotoxins as Tools for the Investigation of Glutamate Receptors

Abstract

Progress in the investigation of glutamate receptors structure and function requires the use of specific chemical tools affecting the responses to glutamate and other excitatory amino acids. Several low molecular weight spider and wasp toxins may be used as valuable tools for identification of certain subtypes of glutamate receptors and the study of their function. Some results obtained on different preparations with the help of argiotoxin 636 (argiopine), neurotoxin isolated from the venom Argiope lobata are reviewed in the present paper.