Glutamate signaling in peripheral tissues

Abstract

The hypothesis that L-glutamate (Glu) is an excitatory amino acid neurotransmitter in the mammalian central nervous system is now gaining more support after the successful cloning of a number of genes coding for the signaling machinery required for this neurocrine at synapses in the brain. These include Glu receptors (signal detection), Glu transporters (signal termination) and vesicular Glu transporters (signal output through exocytotic release). Relatively little attention has been paid to the functional expression of these molecules required for Glu signaling in peripheral neuronal and non-neuronal tissues; however, recent molecular biological analyses show a novel function for Glu as an extracellular signal mediator in the autocrine and/or paracrine system. Emerging evidence suggests that Glu could play a dual role in mechanisms underlying the maintenance of cellular homeostasis -as an excitatory neurotransmitter in the central neurocrine system and an extracellular signal mediator in peripheral autocrine and/or paracrine tissues. In this review, the possible Glu signaling methods are outlined in specific peripheral tissues including bone, testis, pancreas, and the adrenal, pituitary and pineal glands.Keywords: autocrine; glutamate; glutamate receptor; glutamate transporter; neurotransmitter; paracrine; vesicular glutamate transporter; peripheral tissues. Glutamate signaling moleculesGlutamate receptors L-Glutamate (Glu) is accepted as an excitatory amino acid neurotransmitter in the mammalian central nervous system (CNS). Receptors for Glu (GluRs) are categorized into two major classes, metabotropic (mGluRs) and ionotropic (iGluRs) receptors, according to their differential intracellular signal transduction mechanisms and molecular homologies (Fig. 1) [1-3]. mGluRs are further divided into three distinct subtypes containing seven transmembrane domains, including group I (mGluR1 and mGluR5), group II (mGluR2 and mGluR3) and group III (mGluR4, mGluR6, mGluR7 and mGluR8), in line with each receptor's exogenous agonists and intracellular second messengers [4,5]. The group I subtype stimulates formation of inositol 1,4,5-triphosphate and diacylglycerol, while both group II and III subtypes induce reduction of intracellular cyclic AMP (cAMP). On the basis of sequence homology and agonist preference, the latter iGluRs are classified into N-methyl-D-aspartate (NMDA), DL-a-amino-3-hydroxy-5-methylisoxasole-4-propionate (AMPA), and kainate (KA) receptors, which are associated with ion channels permeable to particular cations [6,7].NMDA receptor channels. These channels are highly permeable to Ca 2+ , with sensitivity to blockade by Mg 2+ in a voltage-dependent manner [8,9]. Functional NMDA receptor channels are comprised of heteromeric assemblies between the essential NR1 subunit and one of four different NR2 (A-D) subunits, in addition to one of two different NR3 (A-B) subunits. Expression of the NR2 subunit alone does not lead to composition of functional ion channels in any expression system, while coexpression of...

Consensus meeting: monosodium glutamate – an update

“…Recently, Chevassus et al (2002) gave 10 g MSG or placebo in capsules orally to fasted human subjects at the time they received a 75 g glucose load, and followed the plasma insulin changes over time. There was a significant positive correlation between plasma insulin area-under-thecurve and peak plasma GLU concentrations, suggesting to the authors that GLU enhanced glucose-induced insulin secretion, consistent with the existence of stimulatory GLU receptors on pancreatic beta cells (Hinoi et al, 2004). In this study, peak plasma GLU concentrations were about doubled over baseline and placebo values.…”

Vesicular Glutamate Transporter Immunoreactivity in the Periodontal Ligament of the Rat Incisor

“…Besides the function as a neurotransmitter, glutamate is a general metabolic substrate. The presence of VGluT in non-neuronal tissues such as calcified tissues has been reported (see review Hinoi et al, 2004). Therefore, glutamate has metabotropic effects in the Ruffini endings.…”

Effects of L-amino Acids on Human Peripheral Neutrophil Granulocyte Activation

“…L-glutamate is the most widely investigated amino acid as a signaling molecule [6], having receptors on human lymphocytes [7]. The current in vivo study showed that glutamate concentration increased significantly 90 minutes after breakfast, it reached the values of 2.28 + 1.76 x10 -4 M but it returned near the fasting value at 150 minutes.…”

“…In addition to its important role as a neurotransmitter, glutamate signaling has been described in peripherial tissues, e.g. in bone, pancreas, skin [6]. Furthermore, ionotropic glutamate receptors have been characterized in human lymphocytes [7].…”