Epinephrine, also called adrenaline, is the hormone and neurotransmitter found in many vertebrates responsible for the stress response. It is a catecholamine, meaning it is derived from the amino acid tyrosine and the amino acid phenylalanine [2, 4]. It was originally isolated by Napoleon Cybulski in 1895 and repeat discoveries occurred in May 1896 by William Bates, in 1897 by John Jacob Abel and in 1900 by Jokichi Takamine. Frederich Stolz was the first to artificially synthesize this hormone in 1904 [1].
Figure 1: Chemical and 3D Structure of Epinephrine. (From Wikipedia)Synthesis and Regulation
Epinephrine is synthesized from norepinephrine in a synthetic pathway shared by all catecholamines. However, only the epinephrine secreting cells posses the enzyme phenylethanolamine N-methyltransferase (PNMT) necessary for converting norepinephrine to epinephrine [2, 3]. This is accomplished by the addition of a methyl group donated by S-adenosylmethionine. After synthesis and secretion, epinephrine circulates in the blood bound to the plasma protein albumin [2]. It is a very short lived hormone, with a biological half life of about five minutes. Inactivation occurs in the liver by liver monoamine oxidase, which produces inactive metabolites that appear in the urine [2, 3].
Figure 2: Synthesis Pathway of Catecholamines, Including Epinephrine (From The Kanji Foundry Press)
Regulation of epinephrine is primarily by the sympathetic nervous system. When cholinergic sympathetic nerve fibers in the medulla of the adrenal gland are stimulated it causes local release of acetylcholine. Acetylcholine causes the adrenal medulla chromaffin cells to uptake calcium ions and release epinephrine [2, 4].
Figure 3: Chromaffin cells of the Adrenal Medulla (From The University of Oklahoma Health Sciences Center)Mechanism of Action and Effects
Epinephrine acts through non selective binding of α1, α2, β1, and β2 adrenergic receptors on the cell plasma membrane. In the liver it binds the α1 receptors and starts the inositol-phospholipid signaling pathway [4]. This signals the phosphorylation of glycogen synthase, inactivating it, and phosphorylase kinase, activating it [2, 3]. The activation of phosphorylase kinase activates another enzyme called glycogen phosphorylase, which catalyzes the breakdown of glycogen. Glucose is then released into the bloodstream. β2 receptors are primarily found in skeletal muscle blood vessels and activation of these receptors causes vasodilation. In contrast, α adrenergic receptors are found in most smooth muscles cause vasoconstriction when activated by epinephrine [2, 4].
Epinephrine is perhaps one of the most well known hormones because of its role in the stress response, also known as the “fight or flight” response. When a a stimulus is perceived as a threat or an emergency, epinephrine is released from the adrenal glands and has a number of effects on the body to prepare the organism for an emergency [2, 4]. These effects include:
- Acceleration of heart rate and ventilation rate
- Inhibition of stomach and intestinal action
- Constriction of blood vessels
- Liberation of nutrients for muscular action
- Inhibition of lacrimal gland and inhibition of salivation
- Dilation of pupils
- Relaxation of bladder
- Inhibition of erection
- Auditory exclusion
- Tunnel vision [3, 4]
Figure 4: Binding and Effects of Epinephrine on the Liver (From The Biology Project)Uses
In medicine, epinephrine is used to treat anaphylaxis, a life threatening medical emergency which causes constriction of the airway. Administration of epinephrine prevents worsening of airway constriction and stimulates the heart to continue beating [4]. People with severe allergies which cause anaphylaxis usually carry a dose of epinephrine (typically in a device called an EpiPen) in case of emergencies. You can learn more about anaphylaxis, its symptoms, and epinephrine administration via EpiPen here.
Epinephrine is also used to treat cardiac arrest. It increases peripheral resistance via α1-adrenoreceptor vasoconstriction so that blood is shunted to the heart and lungs and increases the β1-adrenoceptor response which increases cardiac rate and output [4].
References
[1] Donnerer, Josef and Lembeck, Fred. (2006). The Chemical Languages of the Nervous System: History of Scientists and Substances. Basel, Switzerland: Reinhardt Druck.
[2] Norris, David O. (2007). Vertebrate Endocrinology. Burlington, MA, USA: Elsevier Academic Press.
[3] Silverthorn, D. (2007). Human Physiology: An Integrated Approach. San Francisco, USA: Benjamin Cummings.
[4] Stolk, Jon M., U’Prichard, David C., Fuxe, Kjell. (Eds.). (1988). Epinephrine in the Central Nervous System. Oxford: Oxford University Press.
