Amanita research

Bavaria, where in 1937 Ulrich Wieland and Feodor Lynen were able to crystallize for the first time a substance which was called phalloidin that rapidly killed mice after intraperitoneal application. Three years later Heinrich Wieland and Rudolf Hallermayer crystallized from Amanita phalloides extracts a second toxin, amanitin , which with smaller doses killed the experimental animals only after several days Uke a deadly dish of A, phalloides kills humans. Bernhard Witkop (Plate 49) 1940 in H. Wieland s laboratory recognized that phalloidin is a peptide and isolated a new imino acid, allo-hydroxyproline. Then the Second World War interrupted Amanita research which was resumed in Heidelberg by one of the present authors only ten years later and continued in Mainz, Frankfurt and again in Heidelberg through the following decades. 

Contents Introduction. - Mushrooms Causing Death in Rare Cases. Deadly Poisonous Amanita Mushrooms and Their Constituents. - Toadstools Accumulating Amatoxins. - Poisoning by Amatoxins. - Two Centuries of Amanita Research. - Recognition,... 

One peptide toxin from the mushroom Amanita phalhides, a-amanitin, is a specific differential inhibitor of the eukaryotic nuclear DNA-dependent RNA polymerases and as such has proved to be a powerful research tool (Table 37-2). a-Amanitin blocks the translocation of RNA polymerase during transcription. 

Little is formally known about the toxicity of amanita use. Ibotenic acid is a potent neurotoxin, through excitatory amino acid mechanisms (Steiner et al. 1984 Schwarcz et al. 1984). It has been used extensively in animal research to create discrete neuroanatomical lesions. For example, it has been used to lesion the basal forebrain nuclei to create a putative animal model of Alzheimer s disease (Arbogast and Kozlowski 1988). 

The Amanita muscaria mushroom from which muscarine is isolated is also psychoactive. It was believed at first that muscarine was the primary CNS agent. However, more detailed research indicated that muscarine only constituted 0.003% of the fungus. Other species of Inocybe and Clitocybe have more muscarine than muscaria. Other isoxazole components of the muscaria mushroom, such as ibotenic acid and its metabolites, are the main causes of amanita intoxication. This mushroom is believed to have been involved in ancient rituals of the Old World, especially in the Ayrian culture which lived in Siberia around 2000 B.C. This rite worshipped a god called Soma whose presence on earth occurred in the mushroom. Amanita muscaria. Rituals involved brewing a juice with the mushrooms which was consumed by priests. Their urine (isoxazole metabolites) was collected and drunk by others. This ceremony could involve many people and several metabolic rounds until everyone was intoxicated. 

CORBIS, (b)Matt Meadows 45 David Young-Wolff/ PhotoEdit/PictureQuest 46 (l)Amanita Pictures, (r)Richard Megna/Fundamental Photographs/Photo Researchers ... 

Naranjo, P. ayahuasca researcher)—208,237 narcotics, defined—15,104,25 5-7,266,348 Mirrenscbwamm [Amanita muscaria)-- NASA (National Aeronautics and space Administration of U.S. government)—66 na-so le-na [Turbina corymbosa)-iyL National DrugControl [n e] Strategy (1991)— 41,265... 

Research Gliotoxin Cytochalasins Fusicoccin Phalloidin a-Amanitin Trichoderma virens Helminthosporium dermatoideum, etc. Fusicoccum amygdali Amanita phaHoides A. phaHoides Immunosuppressant Anti-actin agents Stomata 1 opening Actin binding RNA polymerase II inhibitor... 

In the mid-1960s investigations carried out independently by four research groups led to the isolation and subsequent structure elucidation from Amanita muscaria, A. strobiliformis, and A. pantherina of three fly-killing and narcosis potentiating compounds muscimol 37-40), ibotenic acid 40-44), and muscazone 43-47). At the same time tricholomic acid, another insecticidal constituent, was found in Tricholoma musca-rium 48,49). The nomenclature commonly accepted for these alkaloids was proposed by Eugster and Takemoto 50). 

The history of the major achievements concerning the isolation, structure elucidation, chemistry, and biological activity of the cyclic peptide principles of A. phalloides was comprehensively covered mainly by T. Wieland, a man of great merit particularly in this branch of natural products research. He dealt with the subject in several review articles 10,87,94,98-101) and more recently in an excellent book on the peptides of poisonous Amanita mushrooms 86). The number of references cited in the book exceeded 750, which gives a rough idea of the proportion of research carried out by chemists on this topic. The scope of the present chapter enables us only to summarize briefly the final results of these interesting studies. 

In Rome peptide research is pursued both at the University La Sapienza (G. Lucente, F. Pinnen, G. Zanotti on cyclic and bicyclic. Amanita-peptides) and at Enricerche, the research laboratory of Enichem (S. Verdini). In Naples E. Benedetti, C. Pedone, P.A. Tamussi and L. Paolillo investigate the conformation of natural and synthetic peptides. 

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