PRINCIPLES OF TOXICOLOGY

physical 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) Toxins
Several toxic marine dinoflagellate species, under particularly favorable conditions for population
growth, cause toxic algal blooms. These “red tides,” so named because water containing high
concentrations of these dinoflagellates sometimes is reddish-colored, can also cause massive mortality
of fish and other marine animals. Algal blooms occur more frequently along coasts that are polluted
by agricultural and human waste. Filter-feeding molluscs are able to concentrate many of these toxins
without being intoxicated. Different kinds of symptoms are produced by eating poisonous clams,
mussels, and other organisms, their nature depends on the toxins involved. Intoxications include
paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), and diarrheic shellfish
poisoning (DSP), which will be discussed below.
One of the most common red tides in the northern hemisphere is due to a dinoflagellate called
Gonyaulax catenella, which secretes a family of over 30 related toxins called saxitoxins, which block
sodium channels. The saxitoxins are classified as paralytic shellfish poisons (PSPs) because their
deleterious actions on the nervous system are reversible, if death is avoided. They only become
dangerous 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 feed
on the poisonous dinoflagellates. It has been shown that these toxins, like the pufferfish toxin
tetrodotoxin, interact with a pore-forming segment on the sodium channel protein alpha-subunit; this
guanidinium toxin binding site has been previously called “ site 1” on the sodium channel (Table
17.2). The mammalian heart sodium channel is pharmacologically different from nerve and skeletal
muscle sodium channels by being about 500 times less sensitive to these toxins, which is probably
fortunate for us!
In 1987, an usual form of neurotoxic shellfish poisoning (NSP) occurred off the coast of Nova
Scotia. The victims experienced amnesia, a loss of ability to recall information. The toxin was found
to be domoic acid, an active analog of the excitatory neurotransmitter glutamic acid. Persistent
activation of glutamate ion channels by this toxin causes neuron degeneration, probably by causing an
excessive influx of calcium ions. DSP is caused by okadaic acid and by ciguatoxin.
Brevetoxins, produced by the dinoflagellate Gymnodinium breve, open, rather than block, sodium
channels (Table 17.2). This organism is found in warmer waters such as are found along the Florida
coastline, and is responsible for massive fish kills every few years. Brevetoxins, like ciguatoxin, are
complicated polycyclic ether molecules that cause the sodium channel to open even under resting
conditions. This causes nerve and muscle cells to spontaneously generate action potentials in the
absence of stimulation, which, of course, is potentially lethal. Since fish are killed by relatively small
amounts of these toxins, humans are not apt to be poisoned by eating exposed fish. However, during
a bloom some of the Gymnodinium become airborne in ocean spray, and people can experience
respiratory distress after inhaling these toxic droplets.
17.6 TOXINS OF HIGHER PLANTS
17.6 TOXINS OF HIGHER PLANTS 417
Mushrooms and Other Fungi
Fewer than 1 percent of the mushroom species are poisonous to humans, but these can be extremely
dangerous. Interest in mushroom hunting is increasing, so it is expected that intoxications will also
increase. Mushrooms of the genus Amanita (Figure 17.3) are the most dangerous. These contain about
equal amounts of two relatively small (seven amino acids) cyclic peptide toxins called amatoxins and
phallotoxins. Unfortunately these cyclic peptides are quite stable at high temperatures, so they survive
cooking. Consumption of a single Amanita phalloides mushroom may be lethal. The amatoxins are