Disease relevance of Anatoxin A

• Blooms of the cyanobacterium Anabaena circinalis are a major worldwide problem due to their production of a range of toxins, in particular the neurotoxins anatoxin-a and paralytic shellfish poisons (PSPs) [1].
• Neurotoxins in axenic oscillatorian cyanobacteria: coexistence of anatoxin-a and homoanatoxin-a determined by ligand-binding assay and GC/MS [2].
• In all methods, Anabaena strains that produced different toxic compounds (e.g. anatoxin-a, microcystin and an unknown neurotoxin) were clustered separately from each other but were grouped either with non-toxic Anabaena and/or Aphanizomenon strains [3].
• Potential developmental toxicity of anatoxin-a, a cyanobacterial toxin [4].
• The most common cyanobacterial neurotoxin is anatoxin-a, and intoxications by these toxins can be fatal through muscular paralysis causing respiratory arrest [5].

Psychiatry related information on Anatoxin A

• We therefore determined the effect of nicotine on the motor activity of adult mice that had been exposed prenatally to anatoxin-a. Pregnant CD-1 mice received either saline vehicle or one of two doses of (+/-) anatoxin-a (125, 200 microg/kg), i.p., on GD13-17 [6].

High impact information on Anatoxin A

• Incubation of Torpedo membranes with anatoxin-a before addition of a radiolabeled channel probe produces a time- and concentration-dependent attenuation of the binding compared to the situation in which anatoxin-a and the probe are added simultaneously [7].
• The time course for the elaboration of this decrease corresponds to electrophysiological measurements of anatoxin-a-induced desensitization of neuromuscular junction responses [7].
• In contrast, the alpha3beta2-selective nAChR antagonist alpha-conotoxin-MII partially inhibited [(3)H]dopamine release from both slice and synaptosome preparations, stimulated with both low (1 microM) and high (25 microM) concentrations of anatoxin-a. Antagonism by alpha-conotoxin-MII was additive with that of alpha7*-selective antagonists [8].
• Comparison of nicotinic drugs in competing for alpha3/beta4 receptor binding sites in this cell line and the binding sites in rat forebrain (predominantly alpha4/beta2 receptors) revealed marked differences in their Ki values, but similar rank orders of potency for agonists were observed, with the exception of anatoxin-A [9].
• This result suggests that anatoxin-a-stimulated exocytosis is mediated by Ca2+ influx via voltage-sensitive Ca2+ channels, with little contribution from Ca2+ entering directly through the nicotinic receptor channel [10].

Chemical compound and disease context of Anatoxin A

• A study was made of the biosynthesis by Anabaena flos-aquae of the tropane-related alkaloid anatoxin-a. Evidence is presented that the toxin arises from ornithine via putrescine (1,4-diaminobutane) and that ornithine decarboxylase (EC 4.1.1.17) is involved [11].
• Anatoxin-a(s) [antx-a(s)] is produced by Anabaena flos-aquae clone NRC 525-17 and is different from anatoxin-a, a known depolarizing agent produced by A. flos-aquae NRC 44-1 [12].

Biological context of Anatoxin A

• Anatoxin-a is a toxin produced from cyanobacterial blooms in freshwaters [13].
• The effects of anatoxin-A on mean arterial pressure (MAP), heart rate, cardiac index (CI), and blood flow (BF) in hindquarter (HQ), renal (R), and mesenteric (M) vascular beds were studied after intravenous (iv) and intracerebroventricular (icv) administration in the conscious rat [14].
• The secretion of catecholamines stimulated by anatoxin-a was completely inhibited in a non-competitive manner by the nicotinic antagonist mecamylamine with an IC50 of 0.4-0.5 microM [15].
• With both methods, high 16S rRNA gene similarity was found among planktic, anatoxin-a-producing Anabaena and non-toxic Aphanizomenon, microcystin-producing and non-toxic Microcystis, and microcystin-producing and non-toxic Planktothrix strains of different geographical origins [16].
• We report here anatoxin-a-induced apoptosis in two non-neuronal cells, viz. cultured rat thymocytes and African green monkey kidney cells (Vero) [5].

Anatomical context of Anatoxin A

• It is concluded that anatoxin-a acts as a potent and selective nicotinic agonist, capable of evoking secretion of endogenous catecholamines from chromaffin cells via their neuronal-type nicotinic receptor [15].
• Thymopentin prepared in 5, 15, and 20% 2-hydroxypropyl-beta-cyclodextrin (HPCD) was able to inhibit guinea-pig ileum contraction stimulated by anatoxin-a (3 x 10(-6) M) after fourteen months of storage at room temperature [17].
• The cyanobacterial alkaloid neurotoxin anatoxin-a was identified in bloom extracts and poisoned dog stomach contents by high-performance liquid chromatography and gas chromatography-mass spectrometry [18].

Associations of Anatoxin A with other chemical compounds

• The anatoxin-a effect, both in human and rat synaptosomes, was antagonized by mecamylamine, alpha-bungarotoxin or methyllycaconitine [19].
• The perfusion of 3.5 mM anatoxin-a increased the extracellular dopamine levels to 701% relative to the basal [20].
• The competition of (-)-[3H]nicotine binding by the enantiomers of nicotine, nornicotine and anatoxin-a in membranes and solubilized preparations of different brain regions of rat [21].
• Strategies to avoid the mis-identification of anatoxin-a using mass spectrometry in the forensic investigation of acute neurotoxic poisoning [22].
• Nicotinic action of anatoxin-a on guinea pig ileum antagonized by thymopentin [23].

Gene context of Anatoxin A

• PSP toxin, anatoxin-a, homoanatoxin-a and microcystins were not detected when pond water from a diseased pond was tested [24].
• Analysis of anatoxin-a by GC/ECD [25].
• Involvement of caspase and reactive oxygen species in cyanobacterial toxin anatoxin-a-induced cytotoxicity and apoptosis in rat thymocytes and Vero cells [5].

Analytical, diagnostic and therapeutic context of Anatoxin A

• Anatoxin-a (AN) and homoanatoxin-a (HMAN) have previously been analysed using high-performance liquid chromatography (HPLC) with UV detection, but this procedure is insufficiently sensitive and is subject to interferences [26].
• Sensitive determination of anatoxin-a, homoanatoxin-a and their degradation products by liquid chromatography with fluorimetric detection [26].
• Mediation of glutamatergic receptors and nitric oxide on striatal dopamine release evoked by anatoxin-a. An in vivo microdialysis study [20].
• A simple and sensitive method for determining anatoxin-a in aqueous samples was developed using solid-phase microextraction (SPME) and gas chromatography with mass spectrometry (GC-MS) detection [27].
• Electromyographic assessment of the neuromuscular blockade produced in vivo by anatoxin-a in the rat [28].

References