The anthelmintic ivermectin has a number of effects on nematodes
which result in changes in behaviour, particularly
locomotion, including paralysis and an inhibition of feeding. This paper
describes the application of an in vitro pharmacological
approach to further delineate the action of ivermectin on feeding behaviour.
Contraction of Ascaris suum pharyngeal
muscle was monitored using a modified pressure transducer system
which detects changes in intrapharyngeal pressure and
therefore contraction of the radial muscle of the pharynx. The pharynx
did
not contract spontaneously. However, serotonin
(5-HT, 100 μm) stimulated rhythmic contractions and relaxations
(pumping) at a frequency of 0·5 Hz. γ-Aminobutyric
acid (GABA) and glutamic acid inhibited the pumping elicited by 5-HT. The
duration of inhibition was concentration
dependent (1–1000 μm) with a threshold of 1 μm
and 10 μm respectively (n=8). Ivermectin
also inhibited pharyngeal
pumping (1–1000 nM). At lower concentrations, ivermectin
(1–10 pM) potentiated the GABA and glutamate inhibition,
so that inhibition occurred at concentrations which were below threshold
in the
absence of ivermectin. These data provide
evidence that the pharynx is a site for the action of ivermectin. Thus
interruption of pharyngeal processes such as, feeding,
regulation of hydrostatic pressure and secretion may provide a new site
of
anthelmintic action.
Internalization of Foldamer-Based DNA Mimics through a Site-Specific Antibody Conjugate to Target HER2-Positive Cancer Cells
