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Functional Assessment of Urinary Neuro-biogenic Amines—A COMPREHENSIVE GUIDE 

99

decrease glutamine uptake by

astroglia (in vitro)

disrupt glucose synthesis by the

astroglia

inhibit the enzyme glutamine

synthetase. Within astroglia

decrease synthesis of tricarboxylic

acid cycle intermediaries necessary

for cellular energy production

Glutamine

PAG NH4

Glutamate

Glutamine

ADP

GS ATP

NH4

NH4

Glutamate

ALDH

Glutamine

NH4 PAG

Glutamate

GAD

GABA

Glu Glu

Glu

Glutamate

Post-synapse

Pre-synapse Glutamate

neuron

Astroglia

Pre-synapse GABA

neuron

TCA

cycle

Post-synapse

GABA

FIGURE 12.

Excitatory amino acid transporters (EAATs) are found on the astroglia and function to keep

extracellular Glutamate levels low.

Legend

: ALDH = succinate semialdehyde dehydrogenase; GAD = glutamate decarboxylase; Glu = glutamate in vesicle; GS = glutamine synthe-

tase; PAG = phosphate‐activated glutaminase; TCA = tricarboxylic acid cycle. Wikimedia Commons image modified by Andrea Gruszecki.

Extracellular glutamate is regulated

by a complex, unique network of re-

lease and reuptake mechanisms. Most

of these mechanisms are rarely depict-

ed in models of glutamate excitatory

signaling. Extracellular glutamate re-

leases occur due to cell membrane cys-

tine-glutamate antiporter (system x

c -

)

exchanges and volume-sensitive organic

anion channels (sodium-dependent Glu

transporters). Extracellular glutamate

may alter activity by binding with ex-

tra-synaptic high-affinity glutamate re-

ceptors, including NMDA and metabo-

tropic glutamate receptors (mGluRs).

N-acetylcysteine upregulates antiporter

system x

c -

in animal studies, but may

be contraindicated in cases of congeni-

tal hypercystinuria. Studies in knockout

mice indicate that a complete failure of

system x

c -

may decrease extracelluar

glutamate in the CNS. Impairment of

the glutamate recycling process facili-

tated by astroglia is considered a major

contributing factor in neuropathology

and is being researched as a causative

factor in neurodegenerative diseases

such as Alzheimer’s, Parkinson’s and

amyotrophic lateral sclerosis (ALS).

In the periphery, current research

suggests that enteric (gastrointestinal)

glia may be important in glutamater-

gic signaling within the gut, and that

neurotransmitter receptors on the gut

mucosa and glial cells may respond to

dietary glutamate and monosodium glu-

tamate (MSG). The stimulation of glu-

tamate receptors in the gut has been

associated with regulation of digestive

processes, the protection of the upper

gastrointestinal tract from low pH con-

ditions, and the stimulation of the af-