Table of Contents Table of Contents
Previous Page  65 / 151 Next Page
Information
Show Menu
Previous Page 65 / 151 Next Page
Page Background

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

57

COMT methylation of catecholamines

may exhaust a cell’s methylation capaci-

ty. Excess DOPA from medications may

increase oxidative stress from MAO and

COMT catabolism and contribute to in-

creased homocysteine levels and periph-

eral neuropathies. High levels of iron

may further increase oxidative stress in

the CNS.

Sulfotransferase (SULT)1A3 catalyz-

es the sulfate conjugation of dopamine.

There are two SULT1A3 genes which

may be expressed and active; this will

affect individual variations in enzyme

activity. SULT1A3 converts dopamine

to dopamine sulfate, which is excreted

in the urine. Sulfotransferase (SULT) en-

zymes are not found in neurons. SULT

activity has been down-regulated in

vitro by coffee compounds, green tea

polyphenols, quercitin and resveratrol.

SULT enzymes also conjugate a variety

of xenobiotic chemicals that may be in-

haled or ingested during environmental

exposures. Elevated levels of metaneph-

rine and normetanephrine may indicate

SULT deficiency.

Inheritance may affect dopamine

synthesis and metabolism, dopamine

receptor function, stress-induced do-

pamine release. Single nucleotide poly-

morphisms (SNPs) in dopamine- and

oxytocin-related genes have been shown

to alter stress-induced dopamine release.

Enzyme deficiencies may be inherited or

acquired from nutritional deficiency or

toxicant exposure.

Receptors

Dopamine activates dopamine re-

ceptors D

1

-D

5

. Dopamine receptors

are expressed at different densities in

the CNS. The neurotransmitter, bound

to its receptor, is the active, function-

al unit. There are many dopamine re-

ceptor subtypes in the brain that affect

behavior, attention, impulse control,

decisions, sleep, and reproductive behav-

iors. Most neurons and peripheral cells

possess receptors for multiple types of

neurotransmitters, and the final cellular

response may be the result of multiple

simultaneous signals. Neurotransmitter

receptors are often the targets of phar-

maceuticals designed to stimulate or in-

hibit dopamine signaling. Dopamine re-

ceptor signaling may affect the behavior

of N-type calcium channels (and other

ionotropic receptors), NMDA receptors,

and GABA-A receptors. Intracellular

signaling pathways affected by dopa-

mine receptors are important in regu-

lating cell cycles, cell proliferation and

homeostasis.

Genetic mutations or SNPs in the

DNA coding for receptor structure may

affect dopamine receptor functions.

In the CNS, alterations in D

2

receptor

expression and CNS density have been

associated with Parkinson’s disease; al-

tered D

1

density has been reported as

systems atrophy progresses. Altered D

1

and D

2

expression has been associated

with Huntington’s disease. SNPs in D

2

,

D

3

, and D

4

receptors have been associ-

ated with schizophrenia and treatment

responses. No changes in dopamine

receptor expression or CNS densi-

ty have currently been associated with

Alzheimer’s dementia.

D

1

receptors

Motor activity, reward, learning,

memory (working memory),

renin secretion, renal function,

blood pressure, vasodilation,

gastrointestinal motility

Stimulates adenylate cyclase

Modulates NMDA receptor

functions