Fasciola hepatica: the effects of neuropharmacological agents upon in vitro motility

The effects of a wide range of neuropharmacological agents on the motility in vitro of Fasciola hepatica have been determined using an isometric transducer system. The neuromuscular blocking agents tubocurarine and decamethonium cause a long-term stimulation of the basal activity of the fluke. Acetylcholine causes an inhibition of activity. This effect is mimicked by the cholinergic agonists carbachol and nicotine, antagonised by the cholinergic blocking agents atropine and mecamylamine, and potentiated by eserine, a cholinesterase inhibitor. With nicotine and atropine the effects are accompanied by an increase in muscle tone at a concentration of 1 X 10(-2) M. Noradrenaline and adrenaline also cause some inhibition of activity, an effect antagonised by guanethidine, which blocks the release of noradrenaline. In contrast, dopamine stimulates fluke motility, whilst its antagonist dihydroergotamine causes an inhibition of activity. The monoamine oxidase inhibitors iproniazid and p-chloromercuribenzoic acid induce a stimulation of activity; with the latter there is an increase in muscle tone at a concentration of 1 X 10(-3) M. The amine depleting agents chloroamphetamine and reserpine, and the monoamine uptake inhibitors desipramine and nortriptyline produce an inhibition of fluke activity, as does the serotonin uptake inhibitor fluoxetine. High concentrations of chloroamphetamine (1 X 10(-2) M) and the uptake inhibitors (1 X 10(-3) M and above) also induce an increase in muscle tone. Serotonin causes a marked stimulation of motility. The pharmacological evidence is consistent with a neurotransmitter role of acetylcholine (inhibitory), dopamine (excitatory), and noradrenaline (inhibitory). The status of serotonin is discussed.