title: Glycine: a new anti-inflammatory immunonutrient.
abstract: The mechanism of the immunosuppressive effects of glycine and its pathophysiological applications are discussed in this review. Glycine has been well characterized in spinal cord as an inhibitory neurotransmitter which activates a glycine-gated chloride channel (GlyR) expressed in postsynaptic membranes. Activation of the channel allows the influx of chloride, preventing depolarization of the plasma membrane and the potentiation of excitatory signals along the axon. Glycine has recently been shown to have similar inhibitory effects on several white blood cells, including hepatic and alveolar macrophages, neutrophils, and lymphocytes. Pharmacological analysis using a GlyR antagonist strychnine, chloride-free buffer, and radiolabeled chloride has provided convincing evidence to support the hypothesis that many white blood cells contain a glycine-gated chloride channel with properties similar to the spinal cord GlyR. Molecular analysis using reverse transcription-polymerase chain reaction and Western blotting has identified the mRNA and protein for the beta subunit of the GlyR in total RNA and purified membrane protein from rat Kupffer cells. Dietary glycine is protective in rat models against endotoxemia, liver ischemia-reperfusion, and liver transplantation, most likely by inactivating the Kupffer cell via this newly identified glycine-gated chloride channel. Glycine also prevents the growth of B 16 melanomas cell in vivo. Moreover, dietary glycine is protective in the kidney against cyclosporin A toxicity and ischemia-reperfusion injury. Glycine may be useful clinically for the treatment of sepsis, adult respiratory distress syndrome, arthritis, and other diseases with an inflammatory component.
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, 27599-7365, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Wheeler
authors.forename: K
authors.initials: K
authors.lastname: Ikejema
authors.forename: N
authors.initials: N
authors.lastname: Enomoto
authors.forename: R F
authors.initials: RF
authors.lastname: Stacklewitz
authors.forename: V
authors.initials: V
authors.lastname: Seabra
authors.forename: Z
authors.initials: Z
authors.lastname: Zhong
authors.forename: M
authors.initials: M
authors.lastname: Yin
authors.forename: P
authors.initials: P
authors.lastname: Schemmer
authors.forename: M L
authors.initials: ML
authors.lastname: Rose
authors.forename: I
authors.initials: I
authors.lastname: Rusyn
authors.forename: B
authors.initials: B
authors.lastname: Bradford
authors.forename: R G
authors.initials: RG
authors.lastname: Thurman
mesh_terms: D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000633:toxicity; D005609:Free Radicals / Q000378:metabolism; D005998:Glycine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006519:Hepatitis, Alcoholic / Q000188:drug therapy; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D015427:Reperfusion Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D012772:Shock, Septic / Q000139:chemically induced / Q000517:prevention & control; D013654:Taurine / Q000494:pharmacology
chemical_list: D000438:Alcohols; D000893:Anti-Inflammatory Agents; D020746:Calcium Channels, L-Type; D018118:Chloride Channels; D005609:Free Radicals; D013654:Taurine; D016572:Cyclosporine; D005998:Glycine