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6

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

Neurotransmitter Transporters

Monoamine transporters are locat-

ed in cell membranes and include spe-

cific transporters for dopamine (DAT),

norepinephrine (NET) and serotonin

(SERT). The transporters move mono-

amines into and out of cells using ion

gradients. The transporters function to

remove neurotransmitters from the syn-

apse (“reuptake”) back into the cell for

storage in vesicles. The neurotransmit-

ters are removed from the cytoplasm

into vesicles by the vesicular mono-

amine transporter (VMAT). Mutations

and single nucleotide polymorphisms

in monoamine transporters may affect

neurotransmitter levels and are being

evaluated for their effects in behavior-

al, mood, attention and neurodegenera-

tive disorders. Inhibition of monoamine

transporters by “reuptake inhibitor”

medications is used in the treatment of

depression, obsessive compulsive disor-

der (OCD), anxiety, chronic pain syn-

drome, and attention deficit hyperactiv-

ity disorder (ADHD). Altered VMAT

density in the brain has been associated

with neurodegenerative conditions.

Neurotransmitter Receptors

Neurotransmitter activity occurs

when a neuro-active molecule binds to

specific receptors on the post-synaptic

nerve. (See Figures 1 & 3.) Receptor

function is as important as neurotrans-

mitter levels; a dysfunctional receptor

may affect biochemistry, mood, behavior

and learning. Receptors are specialized

proteins on neurons. Two main types of

receptors, excitatory and inhibitory, de-

termine the response of a signal-receiv-

ing neuron. A balance between excitato-

ry and inhibitory signaling is necessary

for normal function. Excessive excit-

atory signaling may result in symptoms

such as seizures, excessive inhibitory sig-

naling may result in sedation, anesthesia

or loss of coordination.

The binding of a neurotransmitter to a

receptor activates its function. Receptor

activation may have direct effects on the

nerve cell or activate second messen-

gers. Second messengers may have lo-

cal or systemic effects. The activity of a

nerve cell is determined by the balance

of excitatory and inhibitory signals it re-

ceives. Often, a neurotransmitter may

have the ability to bind to several types

of receptors. Some receptors are “pro-

miscuous” and may bind with multiple

neurotransmitters. Other compounds,

such as hormones and drugs, may also

bind to neurotransmitter receptors. At

least one receptor type, the N-methyl-

D-aspartate receptor (NMDAR), binds

two neurotransmitters simultaneously.

NMDA receptors bind to glutamate,

but also require a glycine cofactor. (See

Figure 3.)

Image courtesy of Wikimedia Commons. Image by RicHard‐59 with Inkscape.

Used with permission.

FIGURE 3.

The binding of a neurotransmitter to its receptor

activates a receptor function, in this example, opening

an ion channel.