trans

NEUROTRANSMITTERS IN PLATYHELMINTHS 387
muscle system, simply because this has been
the most amenable to bioassay.
Putative neurotransmitters in
trematodes and cestodes
Acetylcholine
Acetylcholine has been a candidate inhibitory
neurotransmitter in flatworms since the observation
that cholinergic compounds induce
flaccid paralysis in Fasciola hepatica. Following
this early demonstration of acetylcholine’s
inhibitory action on the liver fluke, there
have been numerous other studies showing
the inhibitory action of acetylcholine on the
musculature of trematodes and cestodes.
Supporting these physiological observations,
histochemical staining for acetylcholinesterase
reveals a striking outline of the majority of flatworm
nervous systems, including the entire
central nervous system and most of the peripheral
nerve plexuses. Antibodies targeting a
choline conjugate support the widespread distribution
suggested by acetylcholinesterase in
the tapeworm Hymenolepis diminuta and the
fluke S. mansoni.
The inhibitory actions of acetylcholine on
flatworm musculature have been demonstrated
on whole animal and muscle strip preparations
derived from a number of different
cestode and trematode species, including
H. diminuta, Dipylidium caninum, S. mansoni
and F. hepatica. Since these studies use either
whole animal or muscle strips, they leave
questions as to the location of the receptors
mediating the inhibitory response. The
response could be mediated by presynaptic
neuronal receptors, receptors on the muscle
itself, or receptors located in many other places
in the preparation. Studies on muscle fibers
isolated from schistosomes demonstrate that
there are inhibitory acetylcholine receptors
located on the muscle membranes; in these
muscle fibers, without neural or paracrine
input, acetylcholine potently inhibits the excitatory
responses mediated by neuropeptides.
Another site of acetylcholine receptors in
schistosomes appears to be the outer surface
of the parasite, at the host–parasite interface.
The role of these acetylcholine receptors in
the biology of the parasite remains unclear,
as do the molecular and biochemical nature
of the tegumental receptors. A comparison of
receptor-binding studies of the tegumental
receptors and physiological contraction assays
suggest that the tegumental receptors are
pharmacologically different from the muscle
receptors.
The pharmacology of flatworm acetylcholine
receptors does not permit their classification
into known subtypes. This is particularly puzzling,
and some responses are associated with
muscarinic (G-protein-coupled) acetylcholine
receptors and some with nicotinic (intrinsic ion
channel) acetylcholine receptors. Muscarinic
and nicotinic cholinergic receptors are structurally
not very closely related to each other,
and the ambiguous pharmacology is unusual.
To provide one example, the muscarinic agonists
arecoline and carbachol are quite effective
inhibitors of flatworm myoactivity (but
muscarine itself is without effect), while the
nicotinic antagonist -bungarotoxin blocks
the cholinergic action. Further, discrepancies
often appear when trying to correlate results
obtained using different preparations. For
example, in schistosomes nicotine reduces
muscle tone and myoactivity in whole animals,
but has no inhibitory effect on isolated
muscle fibers.
Another notable observation amplifying
some of the uncertainty about the role of
acetylcholine in flatworms is the excitatory
action of acetylcholine on muscle fibers from
the free-living flatworm Bdelloura candida. This
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS