trans

NEUROTRANSMITTERS IN NEMATODES 381
species are active in another. A. suum is
commonly used as an experimental model for
testing the effects of neuroactive peptides.
Experiments investigating the action of nematode
FaRPs have shown that these peptides
have potent effects on A. suum somatic muscle
and nerve tissue (Figure 15.17). The application
of PF1, PF2 and PF4 produced muscle
relaxation, while application of PF3, AF3 and
AF4 caused muscle contraction. The FaRPs AF1
and AF2 elicit a biphasic response consisting of
relaxation followed by contraction. Ascaris tissue
responds to experimentally applied FaRPs
derived from both P. redivivus and A. suum.
The wide distribution of some FaRPs (e.g.
AF2 and PF3), and the cross-species efficacy
of others (e.g. PF4), suggests conservation of
FaRP receptors among closely related species.
This observation is consistent with the recent
phylogenetic work that shows that A. suum is
equally closely related to the free-living nematodes
P. redivivus and C. elegans.
Nematode FaRP structure
There are some marked similarities between
the structure of the nematode FaRPs. All the
FaRPs that have been isolated from nematodes
to date are between 7 and 14 amino acids long.
All C terminals end with the RF-NH 2 motif; the
amino acid at position 3 from the C terminal is
methionine, leucine, isoleucine or valine; the
position 4 amino acid is frequently aromatic.
However, despite their similar structure, the
nematode FaRPs show variation in function
that must reflect their constituent amino acids.
To this end, some structure–activity relationships
have been investigated. The structure–
activity relationships so far elucidated illustrate
that rules relating peptide function to structure
vary between FaRPs. The between-FaRP
variation underlines the complexity of the
peptide interactions and suggests that in vivo
FaRP–receptor reactions are highly specific.
Substitution of amino acids in AF1 and
AF2 has revealed that both the N- and the
FIGURE 15.17 Diagram of the receptors that affect the contractility of Ascaris muscle. PF4 opens low (2–5 pS)
conductance Cl channels. GABA opens higher conductance (20–40 pS) Cl channels. Acetylcholine opens 20–50 pS
cation-selective channels. Depolarization opens voltage-dependent Ca 2 channels, VDCaC. AF1 and AF2 activate
receptors that increase the excitability of muscle. AF3 activates receptors that decrease cAMP and also increases
the excitability of muscle. PF1 and PF2 increase cGMP and decrease the excitability of muscle. 5-HT decreases the
excitability of muscle.
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS