{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:28:59Z","timestamp":1784309339568,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA07573"],"award-info":[{"award-number":["AA07573"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA05551"],"award-info":[{"award-number":["AA05551"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Recently, it was demonstrated that liver injury and TNF\u2010a production as a result of endotoxin (lipopolysaccharide, LPS) were attenuated by feeding animals a diet enriched with glycine. This phenomenon was shown to be a result of, at least in part, activation of a chloride channel in Kupffer cells by glycine, which hyperpolarizes the cell membrane and blunts increases in intracellular calcium concentrations ([Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    ) similar to its action in the neuron. It is well known that hepatotoxicity due to LPS has a neutrophil\u2010mediated component and that activation of neutrophils is dependent on increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    . Therefore, the purpose of this study was to determine if glycine affected agonist\u2010induced increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    in rat neutrophils. The effect of glycine on increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    elicited either by the bacterial\u2010derived peptide formyl\u2010methi\u2010onine\u2010leucine\u2010phenylalanine (FMLP) or LPS was studied in individual neutrophils using Fura\u20102 and fluorescence microscopy. Both FMLP and LPS caused dose\u2010dependent increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    , which were maximal at 1 \u03bcM FMLP and 100 \u03bcg\/ml LPS, respectively. LPS increased intracellular calcium in the presence and absence of extracellular calcium. Glycine blunted increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    in a dose\u2010dependent manner with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of ~0.3 mM, values only slightly higher than plasma levels. Glycine was unable to prevent agonist\u2010induced increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    in chloride\u2010free buffer. Moreover, strychnine (1 \u03bcM), an antagonist of the glycine\u2010gated chloride channel in the central nervous system, reversed the effects of glycine (1 mM) on FMLP\u2010 or LPS\u2010stimulated increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    . To provide hard evidence for a glycine\u2010gated chloride channel in the neutrophil, the effect of glycine on radioactive chloride uptake was determined. Glycine caused a dose\u2010dependent increase in chloride uptake into neutro\u2010phils with an ED\n                    <jats:sub>50<\/jats:sub>\n                    of ~0.4 mM, an effect also prevented by 1 \u03bcM strychnine. Glycine also significantly reduced the production of superoxide anion from FMLP\u2010stimulated neutrophils. Taken together, these data provide clear evidence that neutrophils contain a glycine\u2010gated chloride channel that can attenuate increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    and diminish oxidant production by this important leukocyte.\u2014Wheeler, M., Stachlewitz, R. F., Yamashina, S., Ikejima, K., Morrow, A. L., and Thurman, R. G. Glycine\u2010gated chloride channels in neutrophils attenuate calcium influx and superoxide production.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    14, 476\u2013484 (2000)\n                  <\/jats:p>","DOI":"10.1096\/fasebj.14.3.476","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T09:05:51Z","timestamp":1516266351000},"page":"476-484","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Glycine\u2010gated chloride channels in neutrophils attenuate calcium influx and superoxide production"],"prefix":"10.1096","volume":"14","author":[{"given":"MICHAEL","family":"WHEELER","sequence":"first","affiliation":[{"name":"Center for Alcohol Studies University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ROBERT F.","family":"STACHLEWITZ","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SHUNHEI","family":"YAMASHINA","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KENICHI","family":"IKEJIMA","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. LESLIE","family":"MORROW","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"},{"name":"Center for Alcohol Studies University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RONALD G.","family":"THURMAN","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"},{"name":"Center for Alcohol Studies University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2000,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1996.271.1.G97"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199310000-00007"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290335"},{"key":"e_1_2_6_5_1","article-title":"Glycine: a new anti\u2010inflammatory immunonutrient","author":"Wheeler M. 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