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

95

The function of aromatic L-amino

acid decarboxylase (AADC) is the

rate-limiting step for tryptamine syn-

thesis. AADC requires pyridoxal phos-

phate (vitamin B6) as a cofactor. Altered

AADC activity may affect trace amine

levels without affecting the levels of

monoamine neurotransmitters. Altered

AADC activity may, through altered

trace amine levels, affect dopamine

signaling. Activity is dependent on do-

pamine levels, but not specific to do-

pamine. Increased dopamine levels in-

crease AADC activity, which may then

affect other neurotransmitter levels.

There is no evidence that trypt-

amine is stored in vesicles. Trace amines

may pass across cell membranes by

simple diffusion, and their release may

be mediated differently at synapses.

Research continues to identify active

trace amine transport mechanisms in

neurons. Tryptamine is metabolized by

monoamine oxidase A and B (MAO) in

astroglia and neurons. Animal studies in-

dicate that the addition of selenium and

tocopherols to the diet may increase an-

tioxidant capacity and decrease MAO-B

activity. Trace amines and their metabo-

lites are excreted by the kidney in urine.

Receptors:

The trace amine-associated recep-

tors (TAARs) are a recently discovered

class of receptors that respond to vari-

ous trace amines. Most TAARs activity

is the result of second messenger signal-

ing through cyclic adenosine monophos-

phate (cAMP) and protein phosphoryla-

tion. TAARs are found in the CNS and

in the periphery are found in the gas-

trointestinal tract, lung, and kidneys. In

other mammals, some TAARs may serve

as olfactory chemoreceptors and may re-

spond to stimulation by odorous amines.

Research continues into the function

of TAARs and their ligands as not all

TAAR subtypes respond to known trace

amines. Mutations or single nucleotide

polymorphisms in the nine genes coding

for TAARs may increase susceptibility

risk to schizophrenia or bipolar disor-

ders.

In vitro

and

in vivo

studies indicate:

TAAR1

Intracellular expression

Binds to tyramine and PEA with

greatest affinity

may modulate catecholamines

and serotonin by altering cell

membrane transport or receptor

function

Expressed in the CNS and in

leukocytes, gastrointestinal tract,

lung, and kidneys

– has been shown in vitro to

assist leukocyte chemotaxis

towards trace amines; binding

of trace amines to TAAR1 in

leukocytes has been shown

in vitro to promote cytokine

release

Binds with amphetamines and

psychotropic agents (ergot

alkaloids, bromocriptine, lisuride,

D-lysergic acid diethylamide

(LSD), 3,4-methylenedioxy-

methamphetamine [MDMA or

ecstasy])

Interacts with the thyroid

hormone derivative

3-iodothyronamines, which may

affect temperature regulation and

cardiac contractility (in vivo)

TAAR2

Has been shown in vitro to assist

leukocyte chemotaxis towards

trace amines; binding of trace

amines to TAAR2 in leukocytes

has been shown in vitro to

promote cytokine release