{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Choudhary S"],"funding":["NIAID NIH HHS","Bayer Animal Health GmbH","Division of Intramural Research, National Institute of Allergy and Infectious Diseases"],"pagination":["e2111932119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9407656"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(34)"],"pubmed_abstract":["Glutamate-gated chloride channels (GluCls) are unique to invertebrates and are targeted by macrocyclic lactones. In this study, we cloned an AVR-14B GluCl subunit from adult <i>Brugia malayi</i>, a causative agent of lymphatic filariasis in humans. To elucidate this channel's pharmacological properties, we used <i>Xenopus laevis</i> oocytes for expression and performed two-electrode voltage-clamp electrophysiology. The receptor was gated by the natural ligand L-glutamate (effective concentration, 50% [<i>EC<sub>50</sub></i>] = 0.4 mM) and ivermectin (IVM; <i>EC<sub>50</sub></i> = 1.8 nM). We also characterized the effects of nodulisporic acid (NA) on <i>Bma</i>-AVR-14B and NA-produced dual effects on the receptor as an agonist and a type II positive allosteric modulator. Here we report cha"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Nodulisporic acid produces direct activation and positive allosteric modulation of AVR-14B, a glutamate-gated chloride channel from adult <i>Brugia malayi</i>."],"pmcid":["PMC9407656"],"funding_grant_id":["R01 AI155413","NA","R21 AI125899","R21 AI173819","R21 AI092185","R01 AI047194"],"pubmed_authors":["Verma S","Abongwa M","Kashyap SS","Choudhary S","Martin RJ","Robertson AP","Kulke D","Mair GR"],"additional_accession":[]},"is_claimable":false,"name":"Nodulisporic acid produces direct activation and positive allosteric modulation of AVR-14B, a glutamate-gated chloride channel from adult <i>Brugia malayi</i>.","description":"Glutamate-gated chloride channels (GluCls) are unique to invertebrates and are targeted by macrocyclic lactones. In this study, we cloned an AVR-14B GluCl subunit from adult <i>Brugia malayi</i>, a causative agent of lymphatic filariasis in humans. To elucidate this channel's pharmacological properties, we used <i>Xenopus laevis</i> oocytes for expression and performed two-electrode voltage-clamp electrophysiology. The receptor was gated by the natural ligand L-glutamate (effective concentration, 50% [<i>EC<sub>50</sub></i>] = 0.4 mM) and ivermectin (IVM; <i>EC<sub>50</sub></i> = 1.8 nM). We also characterized the effects of nodulisporic acid (NA) on <i>Bma</i>-AVR-14B and NA-produced dual effects on the receptor as an agonist and a type II positive allosteric modulator. Here we report cha","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2026-05-27T20:48:32.951Z","creation":"2025-04-19T13:28:28.526Z"},"accession":"S-EPMC9407656","cross_references":{"pubmed":["35969762"],"doi":["10.1073/pnas.2111932119"]}}