trans

390 NEUROTRANSMITTERS
is phosphorylated, leading to a measurable
increase in glucose utilization and lactate
production.
5-HT produces increased motor activity in a
wide range of flatworms, including important
cestodes such as D. caninum and H. diminuta,
as well as the trematodes S. mansoni and
F. hepatica. When applied to intact animals
and muscle strips, exogenous 5-HT has dramatic
myoexcitatory effects on all flatworms that
have been examined. Application of 5-HT to
S. mansoni in high-Mg 2 solutions produces
contraction, suggesting that the receptors
responsible for the muscle contraction are
present on the muscles themselves, rather
than on the nerve cells. 5-HT has a direct effect
on muscle fibers that have been dispersed
from flatworms, confirming the muscle membranes
as one location of 5-HT receptors in
flatworms. These studies also reveal possible
differences in the nature of 5-HT myoexcitation
in different flatworms. 5-HT alone does
not induce contraction of individual schistosome
muscle fibers; instead it modulates the
contractility of the fibers to other excitatory
agents, such as depolarization or FMRFamiderelated
peptides. However, muscle fibers derived
from free-living flatworms contract in response
to 5-HT alone. Thus, although 5-HT myoexcitation
is uniform throughout the flatworms,
the exact nature of 5-HT-induced myoactivity
remains unclear and may differ among the
flatworms.
The molecular nature of the receptors mediating
these biochemical and physiological
effects remains obscure. The pharmacology
does not allow for a tidy classification of the
receptors into the subtypes derived from
vertebrate pharmacology. In schistosomes,
where there are the most data, the pharmacological
profile associated with the biochemical
effects is very similar to that associated with
the physiological effects. Using either adenylate
cyclase activity in homogenates, or the isolated
muscle contraction assay, the order of
5-HT agonist potency is the same: methiotepin
metergoline ketanserin. Further, the
effect of 5-HT on the muscle fibers is mimicked
by the adenylate cyclase activator
forskolin and blocked by the protein kinase
inhibitor H89. All these data point toward a
common pathway for the activation of adenylate
cyclase in homogenates and the myoexcitatory
activity.
5-HT was the first viable candidate for a
position as a myoexcitatory neurotransmitter
candidate in flatworms, and it remains such.
The wide distribution of 5-HT in flatworms
suggests that it has physiological roles beyond
muscle excitation. Simply, the availability of
contraction assays and the lack of other meaningful
biological assays have kept the focus on
myoexcitation by 5-HT. A fuller understanding
of the role of 5-HT in parasitic flatworms
awaits more relevant bioassays, as well as the
molecular identification and localization of
flatworm 5-HT receptors.
Dopamine, noradrenaline and adrenaline
Dopamine receptors of vertebrates can be
divided pharmacologically into D 1 and D 2
subtypes. Similar subtypes are suggested to be
present in some trematodes, since D 1 agonists
produce a turning–screwing hypermotility,
while D2 agonists produce an arching–curling
hypermotility. D1 antagonists block the turning–
screwing hypermotility associated with the
D1 agonist effects, and the D2 antagonists
depress the effects of the D2 agonists that produce
the arching hypermotility. The concentration
of dopamine in neurons in planarians
is reduced by haloperidol. In Fasciola hepatica
noradrenaline is found in the cephalic region,
and noradrenaline depresses motor activity in
the fluke. Dopamine stimulates motor activity
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS