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

77

requires a magnesium cofactor and

S-adenosylmethionine. COMT is not

found in sympathetic nerves, but mono-

amine oxidase A (MAO-A) is. Contrary

to usual depictions of catecholamine

metabolism, vanillylmandelic acid

(VMA) is primarily produced by the

oxidation of the epinephrine metabo-

lite 3-methoxy-4-hydroxyphenylglycol

(MHPG), and is metabolized by alco-

hol and aldehyde dehydrogenases. The

presence of a beta-hydroxyl group on

epinephrine, norepinephrine and their

metabolites favors reduction by alde-

hyde or aldose reductases. Uptake of

circulating catecholamines by the liv-

er and kidney, while important for the

clearance of catacholamines, contributes

less than 25% of the total metabolism of

catecholamines. Circulating epinephrine

is inactivated by cacatechol-O-meth-

yltransferase (COMT) in the liver. The

clearance of catecholamines from the

blood requires several passes through

the hepatic circulation.

Sulfotransferase (SULT) enzymes

catabolize metanephrine; decreased en-

zyme activity increase metanephrine

levels. SULT enzymes are not found

in neurons. SULT activity has been

down-regulated in vitro by coffee com-

pounds, green tea polyphenols, quercitin

and resveratrol. SULT enzymes also con-

jugate a variety of xenobiotic chemicals

that may be inhaled or ingested during

environmental exposures.

Receptors

Adrenergic receptors bind catechol-

amine neurotransmitters such as norepi-

nephrine and epinephrine.

Alpha (

) adrenergic receptors af-

fect vasoconstriction and gastrointesti-

nal motility. There are multiple adren-

ergic receptor subtypes; each is encoded

separately in the DNA. Alpha receptors

stimulate the production of second mes-

senger molecule 1,4,5-trisphosphate

(IP3), which regulates calcium-medi-

ated functions. Epinephrine binding to

2-adrenergic receptors constricts arter-

ies in the gut, skin, and kidney.

alpha1 receptors – increase smooth

muscle contraction, they contribute the

regulation of sodium re-absorption in

the kidney and glucose metabolism in

adipose tissue and astroglia (astrocytes)

in the nervous system. The receptors

modulate cellular calcium flux and cel-

lular signaling via secondary messenger

molecules.

1 receptors are considered

post-synaptic and stimulatory in the

CNS. Recent evidence indicates that

the receptors may contribute to CNS

locomotor functions. Over-expression

of

1B receptors in a mouse model re-

sults in symptoms of Parkisnon’s disease,

autonomic failure and multiple system

atrophy.

alpha2 receptors – are found on both

pre-a and post-synaptic cells and inhib-

it the release of norepinephrine, acetyl-

choline and insulin. The downregulation

of

-2-adrenoceptors may increase sym-

pathetic nerve outflow and norepineph-

rine levels.

Beta (

) adrenergic receptors signal

cells through cAMP, protein kinase A,

and phosphorylation of proteins. The

binding of epinephrine to

-adrenergic

receptors on liver and adipose cells re-

leases glucose and fatty acids, and relax-

es vascular smooth muscle in the gut,

skin, and kidney. Thyroid function and

T3 levels may increase

-adrenergic re-

ceptor activity.

beta1 receptors – are primarily

found in the heart and kidney. In the

heart, stimulation of

1 receptors

increases heart rate and contractility.