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

113

expression may be inhibited by antide-

pressant medications.

Tyramine is metabolized by both the

A and B forms of monoamine oxidase

(MAO).Animal studies indicate that the

addition of selenium and tocopherols to

the diet may increase antioxidant capac-

ity and decrease MAO-B activity. With

the exception of PEA, trace amines are

considered short-acting and have a half-

life of less than thirty seconds. Tyramine

may be stored in synaptic vesicles; re-

search continues in this area. Most trace

amines are not stored, but disperse by

diffusion through cell membranes. Trace

amines and their metabolites are excret-

ed 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 sig-

naling through cyclic adenosine mono-

phosphate (cAMP) and protein phos-

phorylation. TAARs are found in the

CNS and in the periphery are primarily

found in the gastrointestinal tract, lung,

and kidneys. In other mammals, some

TAARs may serve as olfactory chemore-

ceptors and may respond to stimulation

by odorous amines. Research continues

into the function of TAARs and their li-

gands as not all TAAR subtypes respond

to known trace amines. Mutations or

single nucleotide polymorphisms in the

nine genes coding for TAARs may af-

fect receptor conformation or function,

which may increase susceptibility risk

for schizophrenia or bipolar disorders.

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

Nonsense mutation may

contribute to some cases of

schizophrenia

TAAR5

Function in humans unknown

TAAR6

Expressed in the amygdala of the

brain and in leukocytes, kidneys