title: Actions of the anthelmintic ivermectin on the pharyngeal muscle of the parasitic nematode, Ascaris suum.
abstract: The anthelmintic invermectin 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 microM) stimulated rhythmic contractions and relaxations (pumping) at a frequency of 0.5 Hz. gamma-Aminobutyric acid (GABA) and glutamic acid inhibited the pumping elicited by 5-HT. The duration of inhibition was concentration dependent (1-1000 microM) with a threshold of 1 microM and 10 microM 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.
authors.affiliation: Division of Cell Sciences, School of Biological Sciences, University of Southampton, UK. djab@soton.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Brownlee
authors.forename: L
authors.initials: L
authors.lastname: Holden-Dye
authors.forename: R J
authors.initials: RJ
authors.lastname: Walker
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D017165:Ascaris suum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D017615:Enteric Nervous System / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D018698:Glutamic Acid / Q000494:pharmacology; D007559:Ivermectin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D010609:Pharyngeal Muscles / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000871:Anthelmintics; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007559:Ivermectin