Adrenaline and Noradrenaline — What Are the Differences and Similarities?
Introduction
Adrenaline (Epinephrine), Noradrenaline (Norepinephrine) and Dopamine are amongst a group called catecholamine, which functions as neurotransmitters and hormones within the human body. These three compounds are naturally occurring and are produced in the body. Isoprenaline, unlike the others, is a synthetic catecholamine and is not naturally present in the body. It has an essential pharmacological significance and hence should be mentioned. As the name suggests, it is a catechol group (a benzene ring with two hydroxyl groups) which is attached to an amine group (nitrogen-containing group) as seen in figure 1 from the Rang & Dale’s Pharmacology.
Catecholamine’s key role at rest is thermogenesis (generation of body heat) and nutrient metabolism. Certain catecholamines during a stressful event will favour the body to either defend itself at its full potential or run away from danger. This is known as fight/flight, an evolutionary adaption to survival. These neurotransmitters and hormones stimulate oxygen usage and the consumption of fuels by using free fatty acids and glucose, which causes body heat generation. They also play a role in stimulating glycogenolysis and using the stored fat to break it down to free fatty acids through a process called lipolysis. Catecholamines can regulate the secretion of certain hormones in the body. This has been demonstrated by Dopamine inhibiting Prolactin secretion, Adrenaline which inhibits Insulin secretion and finally Noradrenaline which stimulates the release of Gonadotropin-releasing hormone (GnRH).
Synthesis of catecholamines
Figure 1. Biosynthesis of the catecholamines. From: Rang & Dale’s Pharmacology, 7th edition.
The beginning of the synthesis of catecholamines all starts with an amino acid, L-tyrosine. The biosynthesis sequence goes as follow: Tyrosine -> DOPA (dihydroxyphenylalanine) -> Dopamine -> Noradrenaline (Norepinephrine) -> Adrenaline (Epinephrine).
As seen in figure 1, the tyrosine hydroxylase introduces a hydroxyl group (-OH) into an organic compound. This is a rate-limiting step. The decarboxylase enzyme is responsible for removing a carboxyl group in an organic compound; in this case, the carboxylic acid is removed. The Dopamine beta-hydroxylase will add a hydroxyl group (-OH) on the beta carbon making the compound into Noradrenaline. The finals step is about adding a methyl group from another compound to the amine group on the Noradrenaline. This process is done by taking a methyl group from the two amino acid compound S-Adenosyl-L-methionine (AdoMet) and transferring it to the Noradrenaline, making Adrenaline as a final product.
Where are catecholamines synthesised? There are three central locations that synthesise catecholamine. These are the brain, the adrenal medulla and certain sympathetic nerve fibres. Interestingly, the nerve synthesising catecholamines is dependent on the enzyme present that is part of the biosynthesis. This is seen in dopaminergic neurons, where they only have the first two enzymes (tyrosine hydroxylase and DOPA decarboxylase). Hence, when a dopaminergic neuron gets stimulated, there is a release of Dopamine at the synapse. In terms of the transformation of Noradrenaline to Adrenaline at the adrenal medulla, the enzyme needs to be in the presence of a high local concentration of glucocorticoids from the adrenal cortex. If the chromatin cells (the primary source of circulating catecholamines) are outside the adrenal medulla, they are unable to synthesise Adrenaline.
Differences and similarities
Differences
Adrenaline
Almost exclusively made in the adrenal medulla*.
More Adrenaline is released from the adrenal medulla than Noradrenaline.
Acts mainly as a hormone and is released primarily by the adrenal medulla into the bloodstream. Hence, we can say that Adrenaline is carried throughout the whole body and acts at different organs on different adrenergic receptors.
Synthesised from Noradrenaline.
Activates the alpha and beta-adrenergic receptors, and as such, has a wide-range effect. Relatively non-specific and more or less equal at activating the adrenergic receptors.
Response: constricts minute blood vessels network but dilates blood vessels in the skeletal muscle, increases heart rate and forces of contraction of the heart which increase the cardiac output leading to an increase in blood pressure, increases renin release, bronchodilation from the relaxation of smooth muscles, increase in carbohydrate metabolism (glycogen to glucose and increase glycolysis), increase the utilisation of free fatty acids, increase Glucagon secretion and increase ACTH secretion at the pituitary gland. The metabolic aim is to increase energy usage and availability.
Used in medicine for: severe asthma attacks, anaphylactic shock (acute systemic allergic reaction), glaucoma or eye surgery to maintain dilated pupils, low blood pressure associated with septic shock, cardiac arrest and added to local anaesthetic solutions.
Only released at a stressful moment such as a fight/flight situation and can be released during stress.
Toxicity: sympathomimetic adverse effect. Caution in pregnancy, labour and delivery.
*it is seen that a small amount of Adrenaline is released from the end of the sympathetic neurons and act as a neurotransmitter at the synapse.
Noradrenaline
Predominantly made in the sympathetic nervous system.
More Noradrenaline is released from the sympathetic nervous system than Adrenaline.
Function mainly as a neurotransmitter at the synapse between neurons when released from sympathetic neurons (stored in vesicles). Noradrenaline is released at a small concentration as a hormone in the blood circulation by the adrenal medulla.
Synthesised from Dopamine.
Activates mainly the alpha-adrenergic receptors and acts on beta receptors to a certain degree (seen to act on beta 1 rather than beta 2 but not as strong as the alpha receptors).
Response: increases and maintain blood pressure through peripheral vasoconstriction of blood vessels. Has been noted to stimulate the inotropy of the heart and dilates coronary arteries.
Used in medicine for: emergency low blood pressure used in an acute situation (vasodilatory shock states). These could be from: cardiac arrest, spinal anaesthesia, septicaemia, blood transfusions or drug reactions. Noradrenaline is generally given with an additional agent and can be used in a patient with critical hypotension.
Continuously released as a hormone in the blood circulation at a low dose.
Toxicity: if in overdose and given with another vasopressor, the effect may cause limb ischaemia and limb death.
Similarities
Both are structurally similar except for the additional methyl group seen on the Adrenaline compound.
Both are hormones and both can act as neurotransmitters, but one favours the other and vice versa.
The main physiological action is to initiate a quick, instant and generalised fight-or-flight response. These can be triggered due to a loss of blood pressure, pain, stress, injury, intense emotion or low blood sugar (hypoglycaemia). A response would be tachycardia, increased perspiration, increased blood pressure through narrowing blood vessels, increased blood sugar, anxiety, dilated pupils and tremor.
Both are broken down by catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO).
75% are recaptured and repackaged into vesicles at the nerve endings (especially for Noradrenaline) and 25% is captured by proximal non-neuronal cells. Adrenaline and Noradrenaline in the blood circulation are broken down by the abundant enzymes (COMT/MAO) in the liver.
Bottom line
Noradrenaline: Increase or maintain blood pressure during an acute medical situation. Used for vasodilatory shock states. Mainly produced in the neurons and act as a neurotransmitter. A small amount is made in the adrenal medulla and acts as a hormone.
Adrenaline: Four main actions: increase heart rate and force of contractility, bronchodilation, increase vasoconstriction hence increase blood pressure and finally increase blood glucose availability. Used for anaphylactic shock, emergency asthma attacks, septic shock, cardiac arrest, eye surgery and local anaesthesia. Mainly produced in the adrenal medulla and act as a hormone; hence, has a wide range effect on the body. A small amount is made in the nerves and acts as a neurotransmitter.
Both are released for a fight and flight response for survival adaptation.
Published 20th January 2020. Last reviewed 1st December 2021.
Reference
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