{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:58:58Z","timestamp":1790078338933,"version":"4.0.1"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["NHMRC grant APP1080976"],"award-info":[{"award-number":["NHMRC grant APP1080976"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Between half to 1 million people die annually from malaria. <jats:styled-content style=\"fixed-case\"><jats:italic>Anopheles gambiae<\/jats:italic><\/jats:styled-content> mosquitoes are major malaria vectors. Unfortunately, resistance has emerged to the agents currently used to control <jats:styled-content style=\"fixed-case\"><jats:italic>A.\u00a0gambiae<\/jats:italic><\/jats:styled-content>, creating a demand for novel control measures. The pentameric glutamate\u2010gated chloride channel (GluCl) expressed in the muscle and nerve cells of these organisms are a potentially important biological target for malaria control. The pharmacological properties of Anophiline GluCl receptors are, however, largely unknown. Accordingly, we compared the efficacy of four insecticides (lindane, fipronil, picrotoxin, and ivermectin) on two <jats:styled-content style=\"fixed-case\"><jats:italic>A.\u00a0gambiae<\/jats:italic><\/jats:styled-content> GluCl receptor splice variants with the aim of providing a molecular basis for designing novel anti\u2010malaria treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\"><jats:italic>A.\u00a0gambiae<\/jats:italic><\/jats:styled-content> GluCl receptor b1 and c splice variants were expressed homomerically in <jats:styled-content style=\"fixed-case\"><jats:italic>Xenopus laevis<\/jats:italic><\/jats:styled-content> oocytes and studied with electrophysiological techniques, using two\u2010electrode voltage\u2010clamp.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The b1 and c GluCl receptors were activated with similar potencies by glutamate and ivermectin. Fipronil was more potent than picrotoxin and lindane at inhibiting glutamate\u2010 and ivermectin\u2010gated currents. Importantly, b1 GluCl receptors exhibited reduced sensitivity to picrotoxin and lindane. They also recovered from these effects to a greater extent than c GluCl receptors<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The two splice variant subunits exhibited differential sensitivities to multiple, structurally divergent insecticides, without accompanying changes in the sensitivity to the endogenous neurotransmitter, glutamate, implying that drug resistance may be caused by alterations in relative subunit expression levels, without affecting physiological function. Our results strongly suggest that it should be feasible to develop novel subunit\u2010specific pharmacological agents.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14855","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T19:41:04Z","timestamp":1567539664000},"page":"175-187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The effects of insecticides on two splice variants of the glutamate\u2010gated chloride channel receptor of the major malaria vector, <scp><i>Anopheles gambiae<\/i><\/scp>"],"prefix":"10.1111","volume":"177","author":[{"given":"Mohammed","family":"Atif","sequence":"first","affiliation":[{"name":"Queensland Brain Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph W.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute The University of 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