title: Pharmacological and morphological characteristics of the muscular system of the giant liver fluke (Fascioloides magna - Bassi 1875).
abstract: Motility is required for feeding, reproduction and maintenance of the fluke in the host's liver. According to that, the neuromuscular system can be an attractive drugable target for chemotherapy. Musculature of the Fascioloides magna is organized into three layers, an outer circular layer, beneath this layer the longitudinal layer, and third, the oblique, or diagonal layer underlies the longitudinal layer. In our study, the administration of atropine or caffeine did not cause classic muscle contractions of F. magna muscle strips. However, the Electrical Field Stimulation (EFS) induced stable and repeatable contractions, which enabled us to examine their sensitivity to the various substances. Acetylcholine (ACh) (300 μM and 1 mM), caused only a slight relaxation, without affecting the amplitude of spontaneous contractions or the amplitude of contractions induced by EFS. Contrary to that, atropine (100 μM) caused a significant increase in the basal tone and an increase of EFS-induced contractions. If acetylcholine is an inhibitory neurotransmitter in trematodes, the described effects of atropine are achieved by the blockade of inhibitory neurotransmission. On the other hand, with respect to the process of excitation-contraction coupling, the plant alkaloid ryanodine (30 μM) significantly reduced the basal tone, as well as EFS-induced contractions of F. magna muscle strips. Ryanodine inhibited the potentiating effect of atropine on the basal tone and contractions caused by EFS, which indicates that the contractile effect of atropine is dependent on Ca(++) release from intracellular stores. Caffeine (500 μM) caused relaxation of fluke muscle strips and at the same time significantly enhanced the EFS-induced contractions. Both effects of caffeine can be explained by entry of extracellular Ca(++) into muscle cells. The muscle contractility of F. magna depends both on the entry of extracellular calcium, and calcium release from intracellular stores, which are under the control of RyRs. Our results also suggest that antitrematodal drugs could potentially be developed from substances with selective anti-cholinergic activity.
authors.affiliation: Faculty of Veterinary Medicine, University of Belgrade, Department of Pharmacology and Toxicology, Bulevar Oslobođenja 18, 11000 Belgrade, Serbia. Electronic address: sasa@vet.bg.ac.rs.
authors.forename: Saša M
authors.initials: SM
authors.lastname: Trailović
authors.affiliation: Faculty of Veterinary Medicine, University of Belgrade, Department of Pathomorphology, Bulevar Oslobođenja 18, 11000 Belgrade, Serbia.
authors.forename: Darko
authors.initials: D
authors.lastname: Marinković
authors.affiliation: Faculty of Veterinary Medicine, University of Belgrade, Department of Nutrition and Botany, Bulevar Oslobođenja 18, 11000 Belgrade, Serbia.
authors.forename: Jelena Nedeljković
authors.initials: JN
authors.lastname: Trailović
authors.affiliation: Faculty of Veterinary Medicine, University of Belgrade, Department of Pharmacology and Toxicology, Bulevar Oslobođenja 18, 11000 Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Milovanović
authors.affiliation: Faculty of Veterinary Medicine, University of Belgrade, Department of Pharmacology and Toxicology, Bulevar Oslobođenja 18, 11000 Belgrade, Serbia.
authors.forename: Djordje S
authors.initials: DS
authors.lastname: Marjanović
authors.affiliation: Faculty of Veterinary Medicine, University of Belgrade, Department of Pathomorphology, Bulevar Oslobođenja 18, 11000 Belgrade, Serbia.
authors.forename: Milan R
authors.initials: MR
authors.lastname: Aničić
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D003670:Deer / Q000469:parasitology*; D004558:Electric Stimulation; D005212:Fasciolidae / Q000033:anatomy & histology* / Q000187:drug effects* / Q000502:physiology; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology; D014201:Trematode Infections / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*
chemical_list: D018377:Neurotransmitter Agents; D012433:Ryanodine; D002110:Caffeine; D001285:Atropine; D000109:Acetylcholine
keywords: Acetylcholine; Atropine; Electrical Field Stimulation (EFS); Fascioloides magna