Interaction of carvacrol with the Ascaris suum nicotinic acetylcholine receptors and gamma-aminobutyric acid receptors, potential mechanism of antinematodal action. 2015

Saša M Trailović, and Djordje S Marjanović, and Jelena Nedeljković Trailović, and Alan P Robertson, and Richard J Martin
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia, sasa@vet.bg.ac.rs.

Essential plant oils (or their active principles) are safe to use and a potentially attractive alternative to current antiparasitic drugs. In the present study, we tested the effects of carvacrol on the isolated tissues of Ascaris suum and investigated potential interactions with other antiparasitic drugs. We used somatic muscle flaps for contraction assays, as well as for electrophysiological investigations. Carvacrol 300 μM highly significantly inhibited contractions caused by 1, 3, 10, 30, and 100 μM of ACh (p = 0.0023, p = 0.0002, p = 0.0002, p < 0.0001, and p < 0.0001). The control EC50 for acetylcholine was 8.87 μM (log EC50 = 0.95 ± 0.26), while R max was 2.53 ± 0.24 g. The EC50 of acetylcholine in the presence of 300 μM of carvacrol was 27.71 μM (log EC50 = 1.44 ± 0.28) and the R max decreased to 1.63 ± 0.32 g. Furthermore, carvacrol highly significant potentiates inhibitory effect of GABA and piperazine on the contractions induced by ACh. However, carvacrol (100 and 300 μM), did not produce any changes in the membrane potential or conductance of the A. suum muscle cell. While, 300 μM of carvacrol showed a significant inhibitory effect on ACh-induced depolarization response. The mean control depolarization was 13.58 ± 0.66 mV and decreased in presence of carvacrol to 4.50 ± 1.02 mV (p < 0.0001). Mean control Δg was 0.168 ± 0.017 μS, while in the presence of 300 μM of carvacrol, Δg significantly decreased to 0.060 ± 0.018 ΔS (p = 0.0017). The inhibitory effect on contractions may be the explanation of the antinematodal potential of carvacrol. Moreover, inhibition of depolarizations caused by ACh and reduction of conductance changes directly points to an interaction with the nAChR in A. suum.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D011978 Receptors, Nicotinic One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors. Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D000081007 Cymenes A subclass of monoterpenes that contain a single benzene ring structure with an isopropyl group and one or more methyl groups. Benzenoid Menthane,Benzenoid Menthanes,Cymene,Menthane, Benzenoid,Menthanes, Benzenoid
D000109 Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. 2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000969 Antinematodal Agents Substances used in the treatment or control of nematode infestations. They are used also in veterinary practice. Nematocides,Antinematodal Drugs,Antinematodals,Agents, Antinematodal,Drugs, Antinematodal
D017165 Ascaris suum A species of parasitic nematode usually found in domestic pigs and a few other animals. Human infection can also occur, presumably as result of handling pig manure, and can lead to intestinal obstruction. Ascaris suums,suum, Ascaris
D018079 Receptors, GABA Cell-surface proteins that bind GAMMA-AMINOBUTYRIC ACID with high affinity and trigger changes that influence the behavior of cells. GABA-A receptors control chloride channels formed by the receptor complex itself. They are blocked by bicuculline and usually have modulatory sites sensitive to benzodiazepines and barbiturates. GABA-B receptors act through G-proteins on several effector systems, are insensitive to bicuculline, and have a high affinity for L-baclofen. GABA Receptors,Receptors, gamma-Aminobutyric Acid,gamma-Aminobutyric Acid Receptors,GABA Receptor,gamma-Aminobutyric Acid Receptor,Receptor, GABA,Receptor, gamma-Aminobutyric Acid,Receptors, gamma Aminobutyric Acid,gamma Aminobutyric Acid Receptor,gamma Aminobutyric Acid Receptors
D039821 Monoterpenes Compounds with a core of 10 carbons generally formed via the mevalonate pathway from the combination of 3,3-dimethylallyl pyrophosphate and isopentenyl pyrophosphate. They are cyclized and oxidized in a variety of ways. Due to the low molecular weight many of them exist in the form of essential oils (OILS, VOLATILE). Monoterpene,Monoterpenoid,Monoterpenoids

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