Biology Reference
In-Depth Information
neurotransmitter receptors in nematodes is the cysteine-loop ligand-gated
ion channels (cys-loop LGICs) which comprise both anion and cation
conducting receptors responsible for fast synaptic transmission and
formed by the convergence of five homologous membrane protein
subunits to encase the channel pore.
43
Most knowledge on these ion
channels has been garnered from work on C. elegans which possesses in
excess of 100 LGIC subunit protein encoding genes. This remarkable
subunit complexity facilitates the generation of a diverse array of receptors
that can be gated by a variety of different classical transmitters. Further
complexity derives from the fact that cys-loop LGICs that conduct cations
can be selectively gated by either acetylcholine (ACh) or
g
-aminobutyric
acid (GABA) and those conducting anions can be selectively gated by
ACh, GABA, glutamate or serotonin, providing for a bewildering array of
LGIC receptor subtypes. It is remarkable that C. elegans boasts the greatest
diversity of ionotropic ACh receptor subunits known in any animal.
A relatively constricted, yet diverse, set of 44 putative cys-loop LGICs
were reported from the filarial nematode Brugia malayi
44
with only 19
identified in Trichinella spiralis.
45
The primary excitatory neurotransmitter in nematodes is ACh which
plays a central role in nematode locomotion; the predominant receptors
are muscle-based cys-loop LGICs that resemble classical ionotropic
nicotinic receptors of vertebrates. While we know little of the ionotropic
ACh receptor complements in parasitic nematodes, some differences in
subunit expression have been reported.
46
Pharmacological studies on
anthelmintic action and resistance have generated much of the impetus
for research on these receptors in parasites, with the levamisole- and
pyrantel-sensitive receptors attracting the most intense scrutiny.
47,48
Truncated subunits were identified in three trichostrongylid nematodes
(Haemonchus contortus, Teladorsagia circumcincta, and Trichostrongylus
colubriformis) and correlated with levamisole resistance.
47
The newest
anthelmintics, the amino-acetonitrile derivative monepantel and der-
quantel, the semi-synthetic derivative of paraherquamide, also act at
ionotropic ACh receptors and further stimulate interest in parasite ion
channel biology.
Following the pioneering work of del Castillo and colleagues,
5
a primary inhibitory role in nematode locomotion has been attributed
to GABA through its action on ligand-gated chloride channels (LGCCs).
As with the ionotropic ACh receptors, features including distinct phar-
macology and the actions of the anthelmintic piperazine stimulated
interest in these inhibitory receptors which are now known to display the
subunit diversity that typifies LGICs in nematodes.
43,49
Distinct LGCCs are now believed to be gated by ACh, GABA, and
glutamate as well as various biogenic amines including dopamine,
octopamine, serotonin, and tyramine. A dopamine-sensitive LGCC,
