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Adrenergic Neuron

  • Adrenergic neurons secrete norepinephrine and are found in both the central and autonomic nervous system. Within autonomic fibers, adrenergic neurons are exclusively found in postganglionic neurons of the sympathetic nervous system.
  • Autonomic Nervous System
    • Adrenergic neurons are exclusively found within the sympathetic branch of the autonomic nervous system, specifically within postganglionic fibers. These fibers innervate a large variety of visceral organs and are responsible for subconscious regulation of basic physiological functions (See Sympathetic Nervous System).
  • Central Nervous System
    • Adrenergic neurons within the CNS appear to be responsible for arousal, wakefulness, and elevation mood.
Synthesis and Neurotransmission
  • Overview
    • Norepinephrine is originally synthesized from tyrosine found in the extracellular fluid. Intracellularly transported tyrosine is then modified to norepinephrine which is packaged into vesicles and released following stimulation of the nerve terminal. Once released, synaptic norepinephrine is either degraded enzymatically or re-uptaken into the presynaptic terminal for recycling.
  • Transport
    • Extracellular tyrosine is transported intracellularly via a membrane porter
  • Synthesis and Packaging
    • Cytosolic tyrosine is hydroxylated and converted to "DOPA" by the enzyme Tyrosine Hydroxylase. This reaction represents the rate limiting step of norepinephrine synthesis.
    • Cytosolic DOPA is then converted to dopamine which is subsequently transported into synaptic vesicles using a symporter. This vesicular transport can be inhibited by reserpine
    • Vesicular dopamine is then converted to norepinephrine within the vesicle. Within chromaffin cells of the adrenal medulla, a proportion of the norepinephrine is also converted to epinephrine, explaining why the adrenal medulla secretes both of the adrenergic neurotransmitters
  • Release
    • When an action potential reaches the synapse an influx of calcium ions occurs which triggers the norepinephrine-laden vesicles to fuse to the pre-synaptic membrane and release their contents into the synaptic cleft.
  • Receptor Binding
    • Norepinephrine can bind a variety of adrenergic receptors, each of which is connected to a unique downstream signaling pathway (See: Adrenergic Receptors for more information).
  • Recycling and Degradation
    • Once in the synaptic cleft norepinephrine is either degraded or recycled back into the presynaptic neuron.
    • Degradation is performed by the enzyme COMT and MAO within the synaptic cleft. Pharmacological inhibition of these enzymes can lead to enhanced adrenergic activity, especially within the CNS.
    • Alternatively, synaptic norepinephrine can be re-uptaken into the presynaptic neuron via a number of Norepinephrine Uptake Receptors. Reuptaken norepinephrine is then repackaged within vesicles. A variety of drugs can inhibit these reuptake receptors including Tricyclic Antidepressants and SNRIs, leading to enhanced adrenergic activity, especially within the CNS.