PRINCIPLES OF TOXICOLOGY

Toxic organisms store their toxic substances in specialized organs (plant vacuoles, animal venom
glands) for several reasons. First, the toxic organism otherwise could be exposed to its own poison.
By sequestering the toxin within a membranous sac that is impermeable to the toxin, the other tissues
of the organism can be protected from exposure to the substance or collection of substances (venom).
Second, it is usually advantageous to store the chemical in a concentrated form, which can be efficiently
injected into the victim, with the assistance of a barb or fang. Finally, the venom apparatus must be
connected with an effector system, which senses the presence of the intended victim. In most venomous
animals, the venom is released in response to instructions from the central nervous system, but in some
venomous invertebrates like jellyfishes, the entire sensory and motor apparatus for activating venom
release is built into each venom-emitting cell.
17.3 NATURAL ROLES OF TOXINS AND VENOMS
The functional value of a venom for the procurement of prey or as a defence against predators in most
cases is rather obvious. A venomous predator can immobilize relatively large prey animals, and
consume them at a more leisurely pace. A suitably toxic, but not venomous, plant or animal similarly
avoids consumption. Even if the toxicity of a single individual is not sufficient to protect its own life,
a herbivore or predator will be forced to eat fewer individuals than otherwise, in order to avoid lethal
intoxication. In this manner, survival of the unpalatable species will be enhanced.
In toxic prokaryotic organisms, the biological function of a toxin may not be at all obvious.
Examples that come readily to mind are the dinoflagellate or red tide organisms that occasionally reach
such high population densities in aquatic communities that toxin concentrations in seawater are
sufficient to cause massive fish kills, for instance. It has been suggested that these toxins usually serve
as regulators of cell growth or metabolism and only rarely act as toxins, but these postulated
endogenous functions are yet to be found.
17.4 MAJOR SITES AND MECHANISMS OF TOXIC ACTION
Neurotoxic Actions
17.3 NATURAL ROLES OF TOXINS AND VENOMS 411
Since the nervous system functions primarily as a master communication network that quickly
coordinates the operation of practically all cells, tissues, and organs of the body, it is a prime target for
toxins, which are intended to rapidly alter the functioning of the target organism. Rapid communication
within the nervous system relies on the generation of two types of electrical signal. Initially, small
processes (dendrites) emanating from the neuron’s cell body respond to neurotransmitters released
from adjacent neurons by generating a relatively slow depolarizing junctional potential; this elicits an
action potential, which then rapidly travels to the end of the axon where neurotransmitter is again
released to activate or inhibit some effector cell (Figure 17.1a).
A wide variety of toxins act on electrically active tissues—muscle and neuronal cells—that use
neurotransmitter- and voltage-gated ion channels for generating their electrical signals. The peripheral
nervous and muscular systems are particularly vulnerable cellular targets for rapidly acting toxins,
since no blood–brain barrier protects them from exposure to toxins.
Around 1920 a physiologist named Langley, by locally applying nicotine at only places along the
length of the muscle, first showed that the tobacco alkaloid nicotine acted at a few discrete sites, which
he called receptors, along the length of a muscle cell. Little was known about the molecular properties
of these nicotinic receptors until 1971, when they were purified from a particularly rich source, electric
fishes. Each muscle-like nicotinic receptor is a pentameric complex containing five polypeptide
subunits, which are held together only by noncovalent bonds (Figure 17.1b). Two of the five subunits
are the same. These so-called alpha subunits actually contain the acetylcholine (ACh) binding sites.
Substances such as ACh and nicotine that activate the receptor are called agonists, whereas substances