trans

360 NEUROTRANSMITTERS
CO 2 H
NH 2
GABA
physiology of Ascaris suum (Figure 15.5) as a
basis for explaining the actions of the putative
neurotransmitters.
N
N
Piperazine
FIGURE 15.2 Chemical structure of -aminobutyric
acid (GABA) and the anthelmintic piperazine.
Note the absence of a carboxylic group in piperazine;
the presence of CO 2 increases the potency of piperazine,
presumably by combining with piperazine and
mimicking the action of a carboxylic group.
GABA and produces muscle relaxation by opening
chloride channels; levamisole mimics the
effect of acetylcholine and produces muscle
contraction by opening cation channels; ivermectin
mimics the effect of L-glutamate and
opens glutamate-gated chloride channels and
inhibits nerves and pharyngeal muscle. The
study of the neurotransmitters then, in nematodes,
is encouraged by interest in the mode
of action of anthelmintics, an interest in the
mechanisms of anthelmintic resistance and
also a desire to find new sites of action for
novel drugs. Historically, the study of the mode
of action of these neurotransmitters and
anthelmintics in nematodes has been dominated
by studies on the large intestinal nematode
of the pig, Ascaris suum, and the model
soil nematode, Caenorhabditis elegans. We
examine the neurotransmitters of nematodes
with an emphasis on their site of action (receptor
sites) and effects of related anthelmintic
drugs. The neurotransmitters we consider are:
acetylcholine, GABA, L-glutamate, 5-HT, dopamine,
NO and FMRFamide peptides (Figure
15.4). We start by introducing the anatomy and
Ascaris suum
Jarman, in 1959, described this large, common
porcine parasite for electrophysiological experiments.
Humans are parasitized by a similar
helminth, Ascaris lumbricoides, that is closely
related to A. suum. A. suum is an excellent
experimental model for several reasons: it is
common in the domestic pig population so
it can be readily obtained, post mortem, at
abattoirs; its large size makes it easier to dissect
than the smaller nematode species; and
it is closely related to other parasitic nematodes,
making it a representative model. Recent
evidence suggests that Ascaris is also reasonably
close, phylogenetically, to Caenorhabditis
elegans, allowing genetic information
obtained from C. elegans to be applied to
Ascaris. For all of the above reasons, A. suum
is a useful laboratory model for studies on parasitic
roundworms.
The anatomy of Ascaris suum
Adult ascarids are 20–30 cm long and 5mm
in diameter, which facilitates dissection. Like
other intestinal parasites, Ascaris has a protective
outer cuticlar layer. The cuticle prevents
absorption of hydrophilic compounds, so to
study the effect of hydrophilic compounds on
Ascaris muscle cells, the cuticle is usually
removed. This is done in electrophysiological
studies of the somatic muscle cells, since
access is required to the lumenal side of the
body wall. Since nematodes are effectively a
length of gut encased in a tube of muscle, dissecting
the worm and making a flap preparation,
which exposes the muscle layer, allows
access to the muscle layer. A cross section of
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS