trans

384 NEUROTRANSMITTERS
Davis and Stretton have proposed a tentative
list of five major response types to guide the
search for FMRF receptors in Ascaris. They
examined the electrophysiological effects of
the peptides on the dorsal excitatory motor
neuron, DE2, and the dorsal inhibitory motor
neuron, DI, and they examined the behavioral
effects on injecting the peptides into the body.
Their response types were:
1. Category 1: N-terminally extended – FIRF
amide peptides (AF2, AF7 and AF1) produce
strong behavioral effects
2. Category 2: Produce strong electrophysiological
and behavioral effects (AF2, AF9
and AF8)
3. Category 3: Six peptides with a PGVLR-
Famide group which are encoded on the
same gene, and AF11, which produce strong
behavioral effects, but little effect on DE2
and DI
4. Category 4: Structurally unrelated AF peptides,
with pronounced behavioral effects
and similar electrophysiological effects on
DE2 and DI. AF15 is excitatory but AF17
and AF19 are inhibitory on both the motor
neurons
5. Category 5: Two peptides (AF6 and AF16)
that are weak in their effect on behavior and
electrophysiological effects.
Nitric oxide
As in vertebrates, the gas nitric oxide appears
to be involved as a second messenger/transmitter
in nematodes. The FMRFamides, PF1
and PF2, produce hyperpolarization of muscle
membrane associated with flaccid paralysis. NO
synthase is found in the hypodermis in twice the
amount present in the muscle of A. suum, and
NADH diaphorase, the NO-producing enzyme,
has been demonstrated histochemically in
neurons of A. suum. These observations support
a role for NO in nematodes.
Summary
Despite the apparent anatomical simplicity of
nematodes, with a cylindrical shape and a limited
number of cells making up the nervous
system and muscular system, there is considerable
complexity revealed by the receptors
for a range of classical and peptide transmitters.
Except for glycine the classical transmitters
of vertebrates appear to be present in all
parasitic nematodes. The peptide transmitters,
however, are not identical. The receptors
for the classical and peptide transmitters in
nematodes may have similarities to their vertebrate
counterparts, but their pharmacology
appears to be different. These differences can
be exploited in the design of selective therapeutic
agents.
NEUROTRANSMITTERS IN
PLATYHELMINTHS
Introduction
In the previous section we have illustrated the
connection between some important therapeutic
agents and the receptors for neurotransmitters
in nematodes. We described the
presence of GABA receptors, nACh receptors,
glutamate receptors and the effects of piperazine,
levamisole, pyrantel and ivermectin.
For the treatment of tapeworm and fluke parasite
infestations, the economic pressure for
the development of new therapeutic agents
has not been as great, although major pathogenic
parasites, including Schistosoma mansoni,
cause chronic ill health in humans. Neither
does the study of flatworms have model
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS