1.3.1 Release, Effects and Termination of the Action of Catecholamines

The catecholamines dopamine, L(–)-epinephrine and L(–)-norepinephrine (Figure 1.1-1.3) form a family of neurotransmitters and hormones, which mediate central and peripheral excitation as well as inhibition.

The release of catecholamines occurs in the adrenal medulla and is regulated by preganglionic neurons of the thoracic medulla (T₅ – T₁₁) via cholinergic synapses. Depolarisation of preganglionic axons in humans normally leads to a release of both, epinephrine and norepinephrine in the ratio of about 4 to 1. Under resting conditions only small amounts of epinephrine and norepinephrine are secreted from the adrenomedullary cells.

Figure 1.1: Dopamine Figure 1.2: L(–)-Epinephrine Figure 1.3: L(–)-Norepinephrine

In the case of internal and external stress, caused e.g. by infections, hypoglycemia, hypoxia, hypothermia, thermal burn or pain, secretion of epinephrine and norepinephrine by the adrenal medulla is elevated. The two transmitters provide a state of increased efficiency for the organism by the following mechanisms:

• elevated heart rate and contractility
• bronchial dilatation
• decreased blood supply to the splanchnic bed, the skin and the kidneys
• increased hepatic gluconeogenesis and glycogenolysis
• increased glycogenolysis and lactat synthesis in the skeletal muscles
• elevated lipolysis in adipocytes
• increased cellular glucose uptake
• inhibited insulin secretion by pancreatic islet cells

Catecholamines exert their cellular action by binding to membrane proteins known as adrenergic receptors (see section 1.4). At present, several mechanisms which terminate the action of catecholamines are known  [66] :

1. Diffusion of catecholamines from the biophase to the interstitium, as a gradient-dependent passive mechanism.
2. Uptake into neural and extraneural cellular elements through active transmembrane transport mechanisms.
3. Binding to collagen, elastin, endothelial lining, nuclei and fibroblasts.
4. Oxidative deamination through monoamine oxidase and O-methylation through catechol O-methyl transferase which occur intracellularly.

© 2001 Alexander Binder