Biology Reference
In-Depth Information
designated HcGGR3, was characterized from H. contortus and was found
to be expressed in mechanosensory cells associated with the cervical
papillae.
50
Curiously, quantitative polymerase chain reaction methods
revealed that the transcript for this channel was downregulated in
two ivermectin-selected laboratory strains of H. contortus compared to a
genetically-related unselected strain. Although macrocyclic lactone
treatment seems to apply some form of selective pressure on this channel,
no direct link with anthelmintic resistance has been established. All
H. contortus life stages were also found to express a homologue of the
C. elegans tyramine-gated ionotropic receptor which, following functional
expression, was shown to be sensitive to dopamine, octopamine, and
tyramine.
51
While subunits of many different ionotropic receptors have
been identified in parasites,
49
we are a long way from understanding the
roles they play in parasite biology.
Additional layers of complexity in classical transmitter signaling
include their selective activation of the metabotropic seven trans-
membrane G-protein coupled receptors (GPCRs) that act via guanine
nucleotide-binding proteins (G-proteins), so-called molecular switches
that facilitate the translation of extracellular binding of ligands to intra-
cellular second messenger signaling cascades. G-protein coupled ACh
receptors in nematodes are designated GARs and three subtypes are
known in C. elegans. Data on GARs in parasitic worms are limited to
reports of atypical pharmacology and the characterization of GAR-1 from
A. suum.
52
A number of serotonin GPCRs has been characterized in
C. elegans, but there is little information on homologous receptors in
parasites. Seven biogenic amine receptors were reported from the genome
of B. malayi including three serotonin, two dopamine, and two tyramine/
octopamine receptors.
44,53
The functional expression of a tyramine GPCR
from B. malayi (Bm4) revealed it to be pharmacologically distinct from its
closest C. elegans homologue (TYRA-2).
54
Although in comparison to
C. elegans, a greatly restricted complement of GPCRs were reported from
the root knot nematode Meloidogyne incognita genome,
55
much of this
constriction appears to be due to the absence of olfactory receptors which
form a greatly expanded cohort in C. elegans. In the related species
Meloidogyne hapla, putative receptors for ACh, dopamine, glutamate,
octopamine, serotonin, and tyramine, have been identified.
56
Ascaris
Another important feature of the motor neuron commissures is that
they are branches of identified neurons, and single commissures can be
dissected for biochemical analysis. This dissection was developed by
Carl Johnson,
57
who also devised an assay for choline acetyltransferase
(ChAT, the biosynthetic enzyme for acetylcholine [ACh]) that was
sensitive enough to measure ChAT in single commissures. Dissected
