METABOLIC SYNTHESIS OF
NOREPINEPHRINE AND EPINEPHRINE
Tyrosine (from ECF cytoplasm)
Tyrosine hydroxylase (mitochondrial)
Pyridoxine PO4 (cofactor)
Dopamine B-oxidase (in specific granules)
Mg + ATP
Ascorbic acid (cofactor)
Mechanism whereby Ca brings about the
release of NE
N-methyltransferase (in adrenal medulla)
Ca++ is needed for membrane excitation and release of catecholamines for
adrenergic neurons and adrenal medullary cells.
Synthesis of NE – Tyrosine is transported cytoplasm of
adrenergic neuron DOPA Dopamine.
Storage of NE in Vesicles – Dopamine is transported into
synaptic vesicles using an amine transporter (carrier)
Release of NE – Action potential at nerve ending triggers
calcium influx cytoplasm of neuron causing fusion of
vesicles with cell membrane releasing NE synapse .
Binding to Receptor – NE diffuses across the synaptic
space and binds to either: 1) post-synaptic receptors on
the effector organs or 2) pre-synaptic receptors on the
nerve ending. This triggers a cascade of events resulting in
the formation of intracellular 2nd messenger (cyclic AMP).
Removal of NE – NE diffuses out of the synaptic space
general circulation or it may be recaptured by an uptake
system then back into the neuron.
TERMINATION OF ACTIVITY OF
Reuptake into the neuron (uptake I)
Enzymatic inactivation (MAO, COMT)
Diffusion away from synapse and uptake at extraneuronal sites
(perisynaptic glia and smooth muscle cells) (uptake II)
STORAGE VESICLES OF NOREPINEPRHINE
Rapid turnover of NE
T ½ of 2 hrs.
NE released into synaptic cleft, metabolized by COMT.
Slow turnover of NE
T ½ of 24 hrs.
NE released into neuronal cytoplasm, metabolized by MAO.
Direct-acting (Release of NE
after binding to receptors)
Indirect-acting (Release of
NE followed by binding to
– Blocks the ability of adrenergic neurons to transport NE from the
cytoplasm into storage vesicles.
– Causes ultimate NE depletion in adrenergic neurons, causing
impairment of adrenergic function.
– Effects: Gradual decline in BP
Slows cardiac rate simultaneously
Insomnia, nightmares, hallucinations, depression,
– Blocks the release of stored NE.
– Gradual lowering of BP.
– Displaces NE from storage vesicles – acting as false
Impairs male sexual function