PRINCIPLES OF TOXICOLOGY - Biology East Borneo

17.6 TOXINS OF HIGHER PLANTS 417physical contact of the protozoan with its target cell. Then a pore-forming peptide called amobapore,which causes osmotic swelling and lysis of the target cell, is secreted next to the target cell membrane.Dinoflagellate (Shellfish) ToxinsSeveral toxic marine dinoflagellate species, under particularly favorable conditions for populationgrowth, cause toxic algal blooms. These “red tides,” so named because water containing highconcentrations of these dinoflagellates sometimes is reddish-colored, can also cause massive mortalityof fish and other marine animals. Algal blooms occur more frequently along coasts that are pollutedby agricultural and human waste. Filter-feeding molluscs are able to concentrate many of these toxinswithout being intoxicated. Different kinds of symptoms are produced by eating poisonous clams,mussels, and other organisms, their nature depends on the toxins involved. Intoxications includeparalytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), and diarrheic shellfishpoisoning (DSP), which will be discussed below.One of the most common red tides in the northern hemisphere is due to a dinoflagellate calledGonyaulax catenella, which secretes a family of over 30 related toxins called saxitoxins, which blocksodium channels. The saxitoxins are classified as paralytic shellfish poisons (PSPs) because theirdeleterious actions on the nervous system are reversible, if death is avoided. They only becomedangerous to man when shellfish containing high concentrations of these toxins are consumed.Shellfish are relatively resistant to the saxitoxins, and their tissues retain the toxins as they filter feedon the poisonous dinoflagellates. It has been shown that these toxins, like the pufferfish toxintetrodotoxin, interact with a pore-forming segment on the sodium channel protein alpha-subunit; thisguanidinium toxin binding site has been previously called “ site 1” on the sodium channel (Table17.2). The mammalian heart sodium channel is pharmacologically different from nerve and skeletalmuscle sodium channels by being about 500 times less sensitive to these toxins, which is probablyfortunate for us!In 1987, an usual form of neurotoxic shellfish poisoning (NSP) occurred off the coast of NovaScotia. The victims experienced amnesia, a loss of ability to recall information. The toxin was foundto be domoic acid, an active analog of the excitatory neurotransmitter glutamic acid. Persistentactivation of glutamate ion channels by this toxin causes neuron degeneration, probably by causing anexcessive influx of calcium ions. DSP is caused by okadaic acid and by ciguatoxin.Brevetoxins, produced by the dinoflagellate Gymnodinium breve, open, rather than block, sodiumchannels (Table 17.2). This organism is found in warmer waters such as are found along the Floridacoastline, and is responsible for massive fish kills every few years. Brevetoxins, like ciguatoxin, arecomplicated polycyclic ether molecules that cause the sodium channel to open even under restingconditions. This causes nerve and muscle cells to spontaneously generate action potentials in theabsence of stimulation, which, of course, is potentially lethal. Since fish are killed by relatively smallamounts of these toxins, humans are not apt to be poisoned by eating exposed fish. However, duringa bloom some of the Gymnodinium become airborne in ocean spray, and people can experiencerespiratory distress after inhaling these toxic droplets.17.6 TOXINS OF HIGHER PLANTSMushrooms and Other FungiFewer than 1 percent of the mushroom species are poisonous to humans, but these can be extremelydangerous. Interest in mushroom hunting is increasing, so it is expected that intoxications will alsoincrease. Mushrooms of the genus Amanita (Figure 17.3) are the most dangerous. These contain aboutequal amounts of two relatively small (seven amino acids) cyclic peptide toxins called amatoxins andphallotoxins. Unfortunately these cyclic peptides are quite stable at high temperatures, so they survivecooking. Consumption of a single Amanita phalloides mushroom may be lethal. The amatoxins are