Norepinephrine and Epinephrine: Introduction

Abstract

The catecholamines, norepinephrine and epinephrine (formerly named noradrenaline and adrenaline) are released from the adrenal gland and neurons in the brain. Norepinephrine is also released from the majority of postganglionic, sympathetic neurons in the peripheral (autonomic) nervous system. Conversion of the amino acid, tyrosine, to l‐3,4‐dihydroxyphenylalanine is the rate‐limiting step in the synthetic pathway for both these catecholamines. This process is regulated by several hormones and neurotransmitters, which act via intracellular messengers to help ensure that the rate of catecholamine synthesis matches the rate of their release. In the periphery, norepinephrine and epinephrine are essential for maintaining a stable internal body state (‘homoeostasis’). In the central nervous system, norepinephrine has an important role in the regulation of attention/vigilance/alarm and its synchronization with the autonomic nervous system, but little is known about the function of neuronal epinephrine.

Key Concepts

  • The distribution of norepinephrine and epinephrine in the periphery.
  • The distribution of norepinephrine and epinephrine in and brain.
  • Regulation of the biosynthesis of norepinephrine and epinephrine.
  • The role of norepinephrine and epinephrine in the periphery.
  • The role(s) of norepinephrine and epinephrine in the brain.

Keywords: arousal; attention; catecholamine; epinephrine; dopamine‐β‐hydroxylase; locus coeruleus; lateral tegmental nuclei; norepinephrine; phenylethanolamine‐N‐methyltransferase; tyrosine hydroxylase

Figure 1. The chemical structure of (a) norepinephrine and (b) epinephrine.
Figure 2. A schematic representation of the distribution of norepinephrine‐releasing neurons in the rat brain. The brainstem nuclei that contain neurons that release norepinephrine or epinephrine (C1–C3) are indicated, also. The main projections from the locus coeruleus (A6) form the dorsal bundle, dorsal longitudinal fasciculus and central tegmental tract. Some fibres of the dorsal bundle innervate the thalamus directly, whereas others, together with the central tegmental tract, join the medial forebrain bundle at the level of the caudal hypothalamus. This pathway then projects to many brain areas, including the amygdala nuclei, anterior thalamus, septum, olfactory areas and the neocortex. Fibres from the dorsal longitudinal fasciculus innervate the paraventricular nucleus and, possibly, the supraoptic nucleus in the hypothalamus. The medullary bundle, in which neurons from the locus coeruleus branch from the central tegmental tract, projects to the caudal medulla (not illustrated). Fibres from the central tegmental tract also descend to the spinal cord.
Figure 3. The distribution of the major neuronal projections from the locus coeruleus and lateral tegmental (norepinephrine) systems in the brain.
Figure 4. The synthetic pathway for norepinephrine (NE) and epinephrine (EPI) in neuron terminals and chromaffin cells. The amino acid, tyrosine, derived from the diet, is taken up into catecholamine‐secreting neurons, where it is converted into l‐DOPA in the neuronal cytoplasm. After conversion of l‐DOPA into dopamine, the latter is taken up into the storage vesicles, where it is converted into NE by the enzyme DβH. NE that leaks out of the vesicles is converted into EPI in the cytoplasm of neurons that contain the enzyme, PNMT. Vesicle stores of NE and EPI are maintained by active uptake via a protein transporter in the vesicle membrane.
close

References

Aston‐Jones G and Cohen JD (2005) Adaptive gain and the role of the locus coeruleus‐norepinephrine system in optimal performance. Journal of Comparative Neurology 493 (1): 99–110.

Dalley JW and Stanford SC (1995) Incremental changes in extracellular noradrenaline availability in the frontal cortex induced by naturalistic environmental stimuli: a microdialysis study in the freely moving rat. Journal of Neurochemistry 65 (6): 2644–2651.

Dunkley PR and Dickson PW (2019) Tyrosine hydroxylase phosphorylation in vivo. Journal of Neurochemistry 149 (6): 706–728.

Dunn M , Henke A , Clark S , et al. (2018) Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo. Nature Communications 9 (1): 2838.

España RA , Schmeichel BE and Berridge CW (2016) Norepinephrine at the nexus of arousal, motivation and relapse. Brain Research 1641 (Pt B): 207–216.

Howe PR , Costa M , Furness JB and Chalmers JP (1980) Simultaneous demonstration of phenylethanolamine N‐methyltransferase immunofluorescent and catecholamine fluorescent nerve cell bodies in the rat medulla oblongata. Neuroscience 5 (12): 2229–2238.

Johnson CS , Bains JS and Watts AG (2018) Neurotransmitter diversity in pre‐synaptic terminals located in the parvicellular neuroendocrine paraventricular nucleus of the rat and mouse hypothalamus. The Journal of Comparative Neurology 526 (8): 1287–1306.

McQuade R and Stanford SC (2000) A microdialysis study of the noradrenergic response in rat frontal cortex and hypothalamus to a conditioned cue for aversive, naturalistic environmental stimuli. Psychopharmacology 148: 201–208.

Szabadi E (2013) Functional neuroanatomy of the central noradrenergic system. Journal of Psychopharmacology 27 (8): 659–693.

Tekin I , Roskoski R Jr , Carkaci‐Salli N and Vrana KE (2014) Complex molecular regulation of tyrosine hydroxylase. Journal of Neural Transmission (Vienna) 121 (12): 1451–1481.

Wang Z , Gai Y , Zhou J , Liu J and Cui S (2019) miR‐375 mediates the CRF signaling pathway to regulate catecholamine biosynthesis by targeting Sp1 in porcine adrenal gland. Stress 22 (3): 332–346.

Wong DL (2006) Epinephrine biosynthesis: hormonal and neural control during stress. Cellular and Molecular Neurobiology 26 (4–6): 891–900.

Further Reading

Schwarz LA and Luo L (2015) Organization of the locus coeruleus‐norepinephrine system. Current Biology 25 (21): R1051–R1056.

Stanford SC (1995) Central noradrenergic neurones and stress. Pharmacology & Therapeutics 68 (2): 297–242.

Stanford SC and Heal DJ (2019) Catecholamines: knowledge and understanding in the 1960s, now, and in the future. Brain and Neuroscience Advances 3: 1–11.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Stanford, Susan Clare(Jul 2020) Norepinephrine and Epinephrine: Introduction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000271.pub4]