{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:15:07Z","timestamp":1791504907105,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,11,18]],"date-time":"2003-11-18T00:00:00Z","timestamp":1069113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arch Insect Biochem Physiol"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ligand\u2010gated chloride channels underlie inhibition in excitable membranes and are proven target sites for insecticides. The \u03b3\u2010aminobutyric acid (GABA\n                    <jats:sup>1<\/jats:sup>\n                    ) receptor\/chloride ionophore complex is the primary site of action for a number of currently used insecticides, such as lindane, endosulfan, and fipronil. These compounds act as antagonists by stabilizing nonconducting conformations of the chloride channel. Blockage of the GABA\u2010gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system, convulsions, and death. We recently investigated the mode of action of the silphinenes, plant\u2010derived natural compounds that structurally resemble picrotoxinin. These materials antagonize the action of GABA on insect neurons and block GABA\u2010mediated chloride uptake into mouse brain synaptoneurosomes in a noncompetitive manner. In mammals, avermectins have a blocking action on the GABA\u2010gated chloride channel consistent with a coarse tremor, whereas at longer times and higher concentrations, activation of the channel suppresses neuronal activity. Invertebrates display ataxia, paralysis, and death as the predominant signs of poisoning, with a glutamate\u2010gated chloride channel playing a major role. Additional target sites for the avermectins or other chloride channel\u2010directed compounds might include receptors gated by histamine, serotonin, or acetylcholine.\n                  <\/jats:p>\n                  <jats:p>The voltage\u2010sensitive chloride channels form another large gene family of chloride channels. Voltage\u2010dependent chloride channels are involved in a number of physiological processes including: maintenance of electrical excitability, chloride ion secretion and resorption, intravesicular acidification, and cell volume regulation. A subset of these channels is affected by convulsants and insecticides in mammals, although the role they play in acute lethality in insects is unclear. Given the wide range of functions that they mediate, these channels are also potential targets for insecticide development. Arch. Insect Biochem. Physiol. 54:145\u2013156, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/arch.10112","type":"journal-article","created":{"date-parts":[[2003,11,20]],"date-time":"2003-11-20T13:14:44Z","timestamp":1069334084000},"page":"145-156","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":244,"title":["Chloride channels as tools for developing selective insecticides"],"prefix":"10.1002","volume":"54","author":[{"given":"Jeffrey R.","family":"Bloomquist","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,11,18]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(85)90550-7"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.2570010108"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240051002"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(00)00120-6"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/expr.1998.4316"},{"key":"e_1_2_1_7_1","first-page":"301","article-title":"Toxicology, mode of action, and target site\u2010mediated resistance to insecticides acting on chloride channels","volume":"106","author":"Bloomquist J","year":"1993","journal-title":"Comp Biochem Physiol"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/arch.940260106"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-59549-3_2"},{"key":"e_1_2_1_10_1","first-page":"119","article-title":"The action of avermectin (MK 936) on identified central neurones from Helix and its interaction with acetylcholine and gamma\u2010aminobutyric acid (GABA) responses","volume":"84","author":"Bokisch AJ","year":"1986","journal-title":"Comp Biochem Physiol"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/arch.940220104"},{"key":"e_1_2_1_12_1","unstructured":"ChenG WebsterJ LiJ HuK ZhuJ.2001. 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