trans

392 NEUROTRANSMITTERS
many other animals, the levels of FaRPs in flatworms
appears to be much lower, which may
simply be a reflection of the lower nerve to
body-mass ratio of platyhelminths. These limitations
have dictated the species from which
FaRPs have been structurally characterized.
The only parasitic flatworm from which sufficient
tissue has been gathered is the large
sheep tapeworm Monesia expansa. This cestode
yielded the first flatworm FaRP sequence,
GNFFRFamide. All subsequent flatworm FaRPs
have been identified from free-living flatworms,
where tissue is more readily available: RYIR-
Famide from the predatory terrestrial turbellarian
Artioposhtia triangulata, GYIRFamide
from the freshwater planarian Girardia tigrina,
and both GYIRFamide and YIRFamide
from Bdelloura candida, an ectocommensal
turbellarian of the horseshoe crab. To date,
these four sequences are the only structurally
characterized FaRPs from flatworms.
Flatworm-derived FaRPs are myoexcitatory
in preparations from cestodes and trematodes,
as well as in free-living flatworms. All
three of the FaRPs derived from free-living
flatworms contain the YIRFamide motif, and
all are potently excitatory to muscle strips or
isolated muscle fibers derived from free-living
flatworms and trematodes. The tapeworm
FaRP, GNFFRFamide, also has some activity in
trematode muscle preparations, but it is much
less potent on every preparation examined.
One example is the dispersed muscle preparation
from S. mansoni, where the half-maximal
effects of YIRFamide, GYIRFamide and RYIR-
Famide are somewhere between 1 and 7 nanomolar,
while GNFFRFamide is 500 nanomolar.
The higher potency of peptides derived from
free-living flatworms on trematode muscle
is not surprising, since the trematodes are
descended from and more closely related to
the free-living flatworms than they are to the
cestodes.
Conversely, the cestode-derived GNFFR-
Famide is markedly more potent than the
YIRFamide peptides on cestode muscle. For
example, GNFFRFamide is much more potent
than YIRFamide on muscle strips from M.
expansa, and it more potently stimulates
motility in larval Mesocestoides corti.
It is important to stress that the focus of the
existing data is on the myoactivity of FaRPs
in flatworms, mostly because bioassays of
somatic muscle are presently available. FaRP
distribution throughout the reproductive
structures also suggests that these neuropeptides
might play a role in reproductive function
in flatworms. In fact, FaRP immunoreactivity
increases in the reproductive system innervation
at times of reproductive activity in the
monogenean Polystoma nearcticum. Nerves
associated with the egg chamber express FaRPs
during periods of egg production, but not during
reproductively quiescent periods.
Given their widespread distribution and
potent myoexcitatory activity in every flatworm
examined, FaRPs are a serious candidate
for the role of excitatory neuromuscular transmitter
in the phylum, including both the parasitic
trematodes and cestodes. It is also likely
that FaRPs play other neurotransmitter roles
in flatworms, based on their distribution in
many of the specialized peripheral plexuses.
The immediate challenges are to determine
the precise structure of the FaRPs present in
parasitic worms, and then to identify the
receptors associated with these ligands.
CONCLUSION
In this chapter we have reviewed neurotransmitters
of nematodes and platyhelminths,
recognizing that one of the pressures for the
development of new knowledge in this field is
the requirement of new anti-parasitic drugs
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS