The inhibitory neurotransmitter glycine modulates macrophage activity by activation of neutral amino acid transporters.
نویسندگان
چکیده
Glycine, an important inhibitory neurotransmitter in the mammalian central nervous system (CNS), has been shown to modulate peripheral immune cell responses. In that respect, glycine levels are increased in several neuroinflammatory disorders, such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In this study, we show that glycine modulates macrophage effector functions implicated in CNS inflammation and in other, related inflammatory conditions. We demonstrate that glycine does not affect the production of reactive oxygen species but stimulates myelin phagocytosis and the production of the proinflammatory mediators nitric oxide (NO) and tumor necrosis factor (TNF)-alpha by rat macrophages. These effects of glycine are not mediated by the glycine receptor (GlyR) or by glycine transporters (GlyTs), as neither the GlyR antagonist strychnine nor the antagonist of GlyT1 (ALX5407) reverses the observed effects. In contrast, 2-aminoisobutyric acid, a substrate of neutral amino acid transporters (NAATs), inhibits the glycine-mediated enhancement of myelin phagocytosis as well as of NO and TNF-alpha production. In conclusion, our findings demonstrate that glycine modulates macrophage function through activation of NAATs. Glycine may thereby influence immunological processes in inflammatory diseases involving macrophage activation and demyelination, including MS and related conditions associated with altered glycine levels.
منابع مشابه
Calcitriol modulates the effects of bone marrow-derived mesenchymal stem cells on macrophage functions
Objective(s):Some evidence showed that calcitriol has an important role in regulating growth and differentiation of mesenchymal stem cells (MSCs). However, the interaction between mesenchymal stem cells and macrophage is not clear yet. The current study was done to investigate the in vitro effects of calcitriol on the interactions between bone marrow-derived MSCs and rat macrophages. Material...
متن کاملMolecular basis for differential inhibition of glutamate transporter subtypes by zinc ions.
Zinc ions (Zn2+) are stored in synaptic vesicles with glutamate in a number of regions of the brain. When released into the synapse, Zn2+ modulates the activity of various receptors and ion channels. Excitatory amino acid transporters (EAATs) maintain extracellular glutamate concentrations below toxic levels and regulate the kinetics of glutamate receptor activation. We have investigated the ac...
متن کاملSystem N in eNdothelium.
AMINO ACIDS ARE THE ELEMENTS of protein structure, and their side chains largely determine the function of the proteins they constitute. Some amino acids, such as glycine and glutamate, are important neurotransmitters. Some are metabolized to signaling molecules such as glutamate to -aminobutyric acid (GABA) and arginine to nitric oxide (NO). Amino acids participate in the urea cycle and NH4 me...
متن کاملThe vesicular GABA transporter, VGAT, localizes to synaptic vesicles in sets of glycinergic as well as GABAergic neurons.
A transporter thought to mediate accumulation of GABA into synaptic vesicles has recently been cloned (McIntire et al., 1997). This vesicular GABA transporter (VGAT), the first vesicular amino acid transporter to be molecularly identified, differs in structure from previously cloned vesicular neurotransmitter transporters and defines a novel gene family. Here we use antibodies specific for N- a...
متن کاملHeterogeneous distribution and utilization of inhibitory neurotransmitter transporters
Neurotransmitter homeostasis is important for proper synaptic signal transmission. Synaptically released neurotransmitters are recycled by direct reuptake into the presynaptic terminal and/or uptake into perisynaptic astrocyte processes. In the latter case, most neurotransmitters are metabolized and shuttled back to the presynaptic terminal to restore the neurotransmitter content in that compar...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of neuroscience research
دوره 88 11 شماره
صفحات -
تاریخ انتشار 2010