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

and stroke. Animal studies indicate that

acute stressors may cause transient ele-

vations in extracellular glutamate, and

may temporarily upregulate glutamate

receptor expression. Excess glutamate

may be associated with defective func-

tion of excitatory amino acid transport-

ers (EAATs), glutamine synthetase, the

membrane cystine-glutamate antiporter,

oxidative stress, hypoxia, tissue injury

and increased permeability of the blood

brain barrier (BBB).

Evidence indicates that activation of

serotonin 5-HT2A receptors may in-

crease the release of glutamate and that

psychotic symptoms may occur due to

increased stimulation of amino-3-hy-

droxy-5-methyl-4-isoxazole propionic

acid (AMPA) and kainate glutamate re-

ceptors. AMPA and kainite receptors are

located at the periphery of synapses, and

are not normally stimulated if glutamate

metabolism, release and re-uptake occur

at normal levels.

Synthesis and metabolism:















In the CNS astroglia (astrocytes) re-

lease of a variety of neuroactive mole-

cules (ATP, D-serine, kynurenic acid),

including glutamate, to influence syn-

apse activity. Glial cells are the prima-

ry source of glutamate in the CNS; the

blood-brain barrier (BBB) prevents the

passage of glutamate. Glutamate may

be synthesized by astroglia or in the mi-

tochondria of neurons. Glutamate is in-

ter-converted to glutamine through the

enzymes glutaminase or glutamine syn-

thetase (both enzymes may have mul-

tiple enzyme isoforms). Conversion al-

lows glutamate to be transported into

neurons and astroglia as glutamine.

Once synthesized, glutamate is

stored in the astroglia and in synaptic

vesicles until it is released. Any excess

glutamate released into the synapse is

cleared by highly efficient excitatory

amino acid transporters (EAATs) found

on the astroglia. EEATs, unless dam-

aged or defective, keep extracellular

glutamate levels low and insufficient for

high-affinity glutamate receptor signal-

ing (see Figure 12).

EAAT function is inhibited by reac-

tive oxygen species that are generated

within cells as extracellular glutamate

levels rise. Extracellular glutamate levels

may also increase if glutamine uptake by

cells is compromised.

Exposure to excess manganese, a

necessary trace element, may disrupt

the glutamine/glutamate/GABA cycle.

Manganese may compete with iron for

transport across the blood brain barrier

into the CNS; other transporters may

carry manganese across the BBB as well.

Excess manganese may disrupt mito-

chondrial function, increase oxidative

stress, and deplete glutathione levels.

Manganese tends to concentrate in as-

troglia mitochondria due to the presence

of high-capacity transporters in these

cells. Astroglia contribute glutathione,

and other nutritional support, to neu-

rons. Normal astroglia function is nec-

essary to maintain the BBB. Disruption

of astrogliafunctions may lead to astro-

gliosis and inflammatory signaling in the

CNS. Manganese may: