Catecholamines

George Oliver 1893; Edward Albert Schäfer 1894.

Catecholamines (from Greek catechu = extract from the tiger accia, amine from Greek catecholamines) Ammon = deity, near the temple ammonium chloride was collected as "sal ammoniacus") are a group of biogenic but also synthetically produced amines. The biogenic catecholamines include the substances: dopamine, adrenalin and noradrenalin.

Naturally occurring catecholamines

• Adrenalin
• Noradrenaline
• Dopamine

Synthetic "catecholamines

• Isoprenaline
• Dobutamine
• Dopexamine
• α-Methylnoradrenaline

have a therapeutic significance.

Catecholamines have a stimulating effect on the sympathetic alpha and beta receptors of the cardiovascular system. Dopamine unfolds its central and peripheral effects via dopamine receptors (D-receptors), which can be divided into a D1 and the D2 family. In higher doses, dopamine activates the alpha and beta receptors in addition to the D receptors. Thus, all biogenic catecholamines belong to the group of sympathomimetics. On the one hand, catecholamines act as carriers of the nervous system. On the other hand, they are hormones that are released in the course of stress reactions and thus increase cardiovascular activity. Vanillin mandelic acid, homovanillinic acid and metanephrines are degradation products of catecholamines.

Synthesis: The synthesis of biogenic catecholamines takes place in the adrenal glands, in the CNS and in the postganglionic sympathetic fibres. It takes place via the intermediates: phenylalanine →Tyrosin → DOPA → dopamine → noradrenaline → adrenaline.

Synthesis steps: In detail, phenylalanine is hydroxylated to tyrosine via the enzyme phenylalanine hydroxylase. Tetrahydrobiopterin acts as a cofactor. In a second hydroxylation step, tyrosine is converted by tyrosine hydroxylase to DOPA (3,4-dihydroxyphenylalanine), with tetrahydrobiopterin acting as a cofactor.

In the next step, dopamine is converted from dopa with the help of L-amino acid decarboxylase (also known as DOPA decarboxylase). Here, pyridoxal phosphate (PALP) acts as a cofactor.

In a further step, dopamine is hydroxylated to noradrenalin with the help of dopamine hydroxylase (DBH). Cofactor is vitamin C. In the last possible biosynthesis step, the enzyme phenylethanolamine N-methyltransferase (PNMTase) catalyzes the methylation of noradrenaline to adrenaline. Cofactor in this step is S-adenosylmethionine.

Biogenic catecholamines are found in the brain (dopamine, norepinephrine), as postganglionary sympathetic transmitters (mainly norepinephrine) and as adrenal medullary hormone (mainly adrenaline); catecholamines act via D-receptors (dopamine) or via α and β receptors (norepinephrine, adrenaline).

The transmitter inactivation of noradrenaline and adrenaline takes place on the one hand by elimination from the synaptic cleft and on the other hand by degradation of the transmitters.

Norepinephrine: Three transporters are involved in the transport of norepinephrine from the synaptic cleft: the norepinephrine transporter NAT, the extraneural monoamine transporter EMT and the vesicular monoamine transporter VMAT-2. VMAT-2 causes about 80% of the absorbed norepinephrine to be stored again. Intracellular enzymes are responsible for noradrenaline degradation:

• the mitochondrial monamine oxidase (MAO) and
• the cytoplasmic catechol-O-transferase (COMT).

Adrenaline: Even for released adrenaline, the most important inactivation step is the withdrawal into the neuron. Adrenergic receptors have a transporter similar to the norepinephrine transporter NAT. This transporter is more efficient than the norepinephrine transporter. A smaller part is carried by the extraneural monoamine transporter EMT. The resorption and storage by the vesicular monoamine transporter VMAT-2.

The effects of the catecholamines are mediated via adrenoreceptors. Alpha1-, alpha2-, beta1- and beta2-receptors are receptors that mediate the different effects of norepinephrine and adrenaline, respectively, on the pre- and postsynaptic side.

About 1% of the catecholamines noradrenaline and adrenaline released from the adrenal medulla and the sympathetic nerves are excreted unchanged in the urine. 80-85% of the catecholamine excretion takes place as vanillin mandelic acid and about 15% as metanephrines. If pheochromocytoma is suspected, the determination of free metanephrines in the urine is necessary, since these tumors usually produce large amounts of norepinephrine. The determination of metanephrines is performed in 24-hour urine. In addition, the determination is usually carried out in blood serum.

Normal values:

blood serum:

• Adrenalin: < 80 ng/l (< 4.4 nmol/l)
• Noradrenaline: < 600 ng/l (< 3,6 nmol/l)
• Dopamine: < 150 ng/l (< 0,9 nmol/l)

24-hour urine collection:

• Adrenalin: < 20 µg/24 hrs (< 0.11 µmol/24 hrs (
• norepinephrine: < 105 µg/24 hrs (< 0.62 µmol/24 hrs.)
• Dopamine: < 450 µg/24h (< 2.9 µmol/24 hrs.)
• Vanillin mandelic acid: < 6.5 mg/24 hrs. (< 33 µmol/24 hrs.)
• homovanillic acid: < 7.4 mg/24 hrs. (< 41 µmol/24 hrs.)
• metanephrines: < 1.2 mg/24 hrs. (< 6.3 µmol/24 hrs.)

All normal values listed here are strongly laboratory dependent.

The catecholamines have a chemically analogous structure (they are all phenylethylamines with an ortho-diphenol function, catechol, in the 3,4-position) and are related to adrenaline. The name is derived from the common structural elements: the catecholamine and an amino group in beta position.

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