norepinephrine n : a catecholamine precursor of epinephrine that is secreted by the adrenal medulla and also released at synapses [syn: noradrenaline]
- German: Norepinephrin
Norepinephrine (INN) (abbreviated norepi or NE) or noradrenaline (BAN) is a catecholamine with dual roles as a hormone and a neurotransmitter.
As a stress hormone, norepinephrine affects parts of the brain where attention and responding actions are controlled. Along with epinephrine, norepinephrine also underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle.
However, when norepinephrine acts as a drug it will increase blood pressure, triggering a compensatory reflex that overcomes its direct stimulatory effects on the heart. The reflex, called the baroreceptor reflex, results in a drop in heart rate called reflex bradycardia.
Norepinephrine is synthesized from dopamine by dopamine β-hydroxylase. It is released from the adrenal medulla into the blood as a hormone, and is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons. The actions of norepinephrine are carried out via the binding to adrenergic receptors.
OriginsNorepinephrine is released when a host of physiological changes are activated by a stressful event.
In the brain, this is caused in part by activation of an area of the brain stem called the locus ceruleus. This nucleus is the origin of most norepinephrine pathways in the brain. Noradrenergic neurons project bilaterally (send signals to both sides of the brain) from the locus ceruleus along distinct pathways to many locations, including the cerebral cortex, limbic system, and the spinal cord, forming a neurotransmitter system.
Norepinephrine is also released from postganglionic neurons of the sympathetic nervous system, to transmit the fight-or-flight response in each tissue respectively. The adrenal medulla can also be counted to such postganglionic nerve cells, although they release norepinephrine into the blood.
Norepinephrine systemThe noradrenergic neurons in the brain form a neurotransmitter system, that, when activated, exerts effects on large areas of the brain. The effects are alertness and arousal, and influences on the reward system.
Anatomically, the noradrenergic neurons originate both in the locus coeruleus and the lateral tegmental field. The axons of the neurons in the locus coeruleus act on adrenergic receptors in:
On the other hand, axons of neurons of the lateral tegmental field act on adrenergic receptors in hypothalamus, for example.
This structure explains some of the clinical uses of norepinephrine, since a modification of the system affects large areas of the brain.
MechanismNorepinephrine is synthesized from tyrosine as a precursor, and packed into synaptic vesicles. It performs its action by being released into the synaptic cleft, where it acts on adrenergic receptors, followed by the signal termination, either by degradation of norepinephrine, or by uptake by surrounding cells.
Norepinephrine is synthesized by a series of enzymatic steps in the adrenal medulla from the amino acid tyrosine:
- The first reaction is the oxidation into dihydroxyphenylalanine (L-DOPA) (DOPA = 3,4-DiHydroxy-L-Phenylalanine), catalyzed by tyrosine hydroxylase. This is the rate-limiting step.
- This is followed by decarboxylation into the neurotransmitter dopamine, catalyzed by pyridoxal phosphate & DOPA decarboxylase.
- Last is the final β-oxidation into norepinephrine by dopamine beta hydroxylase, requiring ascorbate as a cofactor (electron donor).
Vesicular transportBetween the decarboxylation and the final β-oxidation, norepinephrine is transported into synaptic vesicles. This is accomplished by vesicular monoamine transporter (VMAT) in the lipid bilayer. This transporter has equal affinity for norepinephrine, epinephrine and isoprenaline.
ReleaseTo perform its functions, norepinephrine needs to be released from synaptic vesicles. Many substances modulate this release, some inhibiting it and some stimulating it.
For instance, there are inhibitory α2 adrenergic receptors presynaptically, that gives negative feedback on release by homotropic modulation.
- Further reading: Adrenergic receptor