THE POSSIBLE ROLE OF ACETYLCHOLINE IN SCHISTOSOMA MANSONI

Abstract

It has been demonstrated that extracts of Schistosoma mansoni contain high acetylcholinesterase and choline acetylase activities (Bueding, 1952). Subsequently, acetylcholine esterase and choline acetylase activities were found by Chance & Mansour (1953) in another trematode, the liver fluke Fasciola hepatica. Furthermore, it has been reported that Fasciola hepatica contains an acetylcholine-like substance and that a variety of cholinomimetic agents exert an inhibitory effect on the muscular activity of this parasite (Chance & Mansour, 1953). Similarly, inhibitory effects of some cholinomimetic agents on the motor activity of Schistosoma mansoni have been observed (Bueding, 1962). This report deals with motor responses of Schistosoma mansoni to cholinomimetic and other pharmacological agents and with experiments designed to determine the presence of acetylcholine in this parasite. Observations are reported indicating that cholinomimetic agents and cholinesterase inhibitors produce a paralysis of the worms, which is reversed by certain antagonists of acetylcholine-like drugs. Furthermore, S. mansoni contains a material the properties of which are similar to those of acetylcholine. METHODSIndividual adult worm pairs of Schistosoma mansoni (Puerto Rican strain) were incubated in 75%,' horse serum in distilled water at 37' C in cylindrical glass vessels (17 mm inside diameter, 12 mm high). Motility of the worms was observed under a dissecting microscope at predetermined time intervals (5 min, 15 min, thereafter every 15 min, for 1 hr, and thereafter every hour for two to four hours). At least four worm pairs (i.e., four males and four females) were used at any given concentration of a tested compound. Normal motor activity consisted of waves of contraction along the entire body, with occasional whipping motion and of frequent contractions of the oral sucker and acetabulum. Activity of the acetabulum may also result in adhesion to the bottom of the vessel with occasional moving along the glass. Paralysis and stimulation are readily observable deviations from this motor behaviour. The activity of control worms in 75% horse serum did not change significantly during 5 hr, the maximum period of observation.With two exceptions (see below) all compounds were added in an aqueous solution to 0.75 ml. of horse serum and enough distilled water was added to bring the total volume to 1.0 ml. The two water-insoluble compounds, 0,0-dimethyl-0-(2,4,5-trichlorophenyl) phosphorothioate (Ronnel) and its oxygen analogue (McCollister et al., 1959) were dissolved in 95% ethanol and 0.02 ml. of this solution were added to a mixture of 0.75 ml. of horse serum and 0.23 ml. of water. The motor activity of schistosomes was not affected in 2% ethanol.

Synthesis, Bioactivity Evaluation, and Toxicity Assessment of Novel Salicylanilide Ester Derivatives as Cercaricides against Schistosoma japonicum and Molluscicides against Oncomelania hupensis

“…The principal physiological role of AChE is believed to be termination of transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter (ACh) (36). ACh and AChE have been demonstrated to be involved in the motor activity of the schistosome (37)(38)(39)(40)(41). Their presence has been established at several developmental stages of the parasite, including cercaria, schistosomula, and adult worm.…”

The pharmacology of the cholinoceptor in muscle preparations of Ascaris lumbricoides var. suum

“…Nicotine-like drugs have been shown to induce flaccid paralysis in the trematode, Schistosoma mansoni (Barker, Bueding & Timms, 1966). Muscarine-like drugs were without activity.…”

Inhibition by metrifonate and dichlorvos of cholinesterases in schistosomes

“…Conversely, a subsequent return of enzyme activity was associated with a return of the worms to the mesenteric veins. Since there is evidence for a physiological role of acetylcholine in schistosomes (Bueding, 1952;Barker et al, 1966) and since administration of another antischistosomal compound, i.e., p-rosaniline, results in an inhibition of AChE activity of S. mansoni (Bueding et al, 1967), it is possible that AChE inhibition produces functional damage to the worm.…”

“…Since many organophosphorus compounds are potent inhibitors of various cholinesterases and since there is evidence that acetylcholine may be a humoral neurotransmitter in Inhbition of schistosme cholinesterases schisto (Somes (3ueding, 1952;Barker, Bueding & Timms, 1966) on schistosome cholinesterases were studied. It was found that differences in the chemotherapeutic activities of metrifonate in human subjects infected with S. haematobiwm, on the one hand, and with S. mansoni on the other, could not be accounted for by differences in the inhibitory potency of metrifonate on the enzymes catalyzing the hydrolysis of acetylcholine in the two species of trematodes.…”