trans

NEUROTRANSMITTERS IN PLATYHELMINTHS 391
in Fasciola hepatica, but in Schistosoma mansoni
dopamine produces an inhibitory effect
on longitudinal and circular muscles.
Other putative neurotransmitters
In addition to the candidates considered thus
far, there are a number of other compounds
which may be neurotransmitters in flatworms,
some examples being nitric oxide and histamine.
In each of these cases, the information
about the presence and role of these compounds
is quite sketchy, so they will not be
considered in great detail here.
A role of nitric oxide (NO) as a diffusible
transmitter is suggested by NADPH diaphorase
staining, which has been reported in the nervous
systems of many flatworms, including
the trematode S. mansoni and the cestodes
H. diminuta, D. dendriticum and Mesocestoides
corti. The staining is prominent in the nerve
cords in each case, and sometimes includes
nerves that appear to serve sensory structures
in the tegument. Nitric oxide synthase (NOS)
activity has been detected in homogenates of
the tapeworm H. diminuta. In addition to the
possibility that NO plays a role in worm physiology,
there is the possibility that NO has a role
in the host–parasite relationship. One response
of schistosome-infected hosts might be to
stimulate inducible NOS via IFN-, and that
this might lead to the elimination of lungstage
somules. Conversely, it has been suggested
(without significant supporting data)
that schistosomes might use NO to alter the
vasculature of the host.
The data regarding the presence of histamine
in various flatworms do not create a
clear pattern, with some worms apparently
lacking histamine altogether and others with
seemingly high concentrations. One puzzling
example is the tapeworm H. diminuta, which
allows exogenous histamine to diffuse across
the outer surface, but does not itself synthesize
histamine. Histamine has no (or very
little) observable effect in most of the flatworm
bioassays. One exception to this is
S. mansoni cercariae, where H1 receptor antagonists
immobilize the free-swimming stages,
and high concentrations of exogenous histamine
can block the immobilization. Therefore,
the evidence that histamine serves as a neurotransmitter
in platyhelminths is still rather
scanty.
FMRFamides
Attention has recently focused on neuropeptides
as neurotransmitter candidates in platyhelminths.
This attention originated with
studies in the 1980s demonstrating immunoreactivity
to a plethora of antisera raised against
neuropeptides from other animals. Amongst
a number of potential neurotransmitters, the
most data have accumulated supporting a role
for short amidated peptides similar to the
molluscan cardioexcitatory peptide Phe-Met-
Arg-Phe-amide (using single letter annotation,
FMRFamide). These peptides will be collectively
referred to here as FaRPs, FMRFamiderelated
peptides.
Extensive FaRP immunoreactivity is present
throughout the central and peripheral nervous
system of every flatworm thus far examined
(more than 40 species), including the
plexuses associated with the somatic musculature,
the reproductive structures, the holdfast
organs and the alimentary system. The
immunoreactivity suggests that FaRP distribution
largely mirrors that of acetylcholine.
Despite the widespread distribution of FaRP
immunoreactivity, the structural identification
of FaRPs in parasitic flatworms has been
difficult. The largest impediment to biochemical
purification has been amassing sufficient
quantities of tissue. Also, in comparison to
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS