Functional characterization of three G protein-coupled acetylcholine receptors in parasitic nematode Trichinella spiralis - Anses - Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail Accéder directement au contenu
Article Dans Une Revue International journal for parasitology. Drugs and drug resistance Année : 2023

Functional characterization of three G protein-coupled acetylcholine receptors in parasitic nematode Trichinella spiralis

Résumé

The physiological significance of metabotropic acetylcholine receptors in parasitic nematodes remains largely unexplored. Here, three different Trichinella spiralis G protein-coupled acetylcholine receptors (TsGAR-1, -2, and -3) were identified in the genome of T. spiralis. The phylogenetic analyses showed that TsGAR-1 and -2 receptors belong to a distinct clade specific to invertebrates, while TsGAR-3 is closest to the cluster of mammalian-type muscarinic acetylcholine receptors (mAChR). The mRNA of TsGAR-1, -2, and -3 was detected in muscle larvae, newborn larvae, and adults. The functional aequorin-based assay in Chinese hamster ovary cells revealed that all three types of T. spiralis GARs trigger the Gq/11 pathway upon activation of the receptor with the acetylcholine ligand. TsGAR-1 and TsGAR-2 showed atypical affinity with classical muscarinic agonists, while TsGAR-3 was sensitive to all muscarinic agonists tested. High concentrations of propiverine antagonist blocked the activities of all three TsGARs, while atropine and scopolamine antagonists effectively inhibited only TsGAR-3. Our data indicate that the distinct pharmacological profile of TsGAR-1 and -2 receptors, as well as the phylogenetic distance between them and their mammalian orthologs, place them as attractive targets for the development of selective anthelmintic drugs interfering with nematodes’ cholinergic system.
Fichier principal
Vignette du fichier
2023_Ning_Int_J_Parasitol.pdf (12.22 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Licence : CC BY - Paternité

Dates et versions

anses-04309487 , version 1 (09-04-2024)

Licence

Paternité

Identifiants

Citer

Caina Ning, Aurélie Heckmann, Lourdes Mateos-Hernández, Grégory Karadjian, Ladislav Šimo. Functional characterization of three G protein-coupled acetylcholine receptors in parasitic nematode Trichinella spiralis. International journal for parasitology. Drugs and drug resistance, 2023, 23, pp.130-139. ⟨10.1016/j.ijpddr.2023.11.005⟩. ⟨anses-04309487⟩
54 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More