Adrenaline Presentation

Adrenaline
Adrenaline ( Also known as

Epinephrine)
 Epinephrine is a catecholamine produced in the final step of conversion of tyrosine.
 Fight or flight hormone
 It is hydrophilic and therefore unable to diffuse directly across the cell membrane
 Non-selective agonist of alpha-adrenoceptors and beta-adrenoceptors
 The complete cycle is evident when tyrosine is gradually converted by various
enzymes into L-Dopa, then dopamine, then norepinephrine, and finally epinephrine.
 Factors involved in regulation of tyrosine will affect the levels of epinephrine in the
same way as for dopamine and norepinephrine.
 Enzymes that break down this neurotransmitter are present in the synapse, as well as
inside neurons and they include catechol-O-methyltransferase ( COMT ) and
monoamine oxidase ( MAO ).
 Epinephrine does not have its own receptors, instead its chemical composition resembles that of
norepinephrine very closely.
 Epinephrine stimulates norepinephrine receptors both in the brain as well as peripherally.
 There are two major classes of receptors for norepinephrine and epinephrine i.e alpha-
adrenoceptors and beta-adrenoceptors
 Epinephrine is metabotropic i.e it uses second messengers for signal transfer from cell surface to
the cytoplasm.
 norepinephrine is primarily a neurotransmitter while epinephrine is primarily a hormone.
 Effects of epinephrine stimulation are evident during stress reactions, and its one of the major
hormones that stimulate the sympathetic nervous system.
 Stimulation of adrenergic receptors is likely to exert sympathetic effects while blocking those
receptors will result in parasympathetic reactions.
 Some dangerous compounds like ephedrine exert stimulatory effects by binding to a variety of
catecholinergic receptors, including those usually stimulated by adrenaline.
Epinephrine Synthesis and Release
 Epinephrine is synthesized from norepinephrine within the adrenal medulla,

which are small glands associated with the kidneys
 Preganglionic fibers of the sympathetic nervous system synapse within the
adrenals
 Activation of these preganglionic fibers releases acetylcholine, which binds to
postjunctional nicotinic receptors in the tissue.
 This leads to stimulation of NE synthesis within adenomedullary cells, but
unlike sympathetic neurons, there is an additional enzyme
(phenylethanolamine-N-methyltransferase) that adds a methyl group to the
NE molecule to form epinephrine
 The epinephrine is released into the blood perfusing the glands and carried
throughout the body.
Neurotransmission
 The amino acid tyrosine is transported into the sympathetic nerve axon
 Tyrosine is converted to DOPA by tyrosine hydroxylase ( rate limiting step for norepinephrine synthesis)
 DOPA is converted to dopamine by DOPA decarboxylase
 Dopamine is transported into vesicles then converted to norepinephrine by dopamine beta-hydroxylase.
This transport into vesicles is blocked by the drug reserpine.
 An action potential traveling down the axon depolarises the membrane and causes calcium to enter the
axon.
 Increased intracellular calcium causes the vesicles to migrate to the axonal membrane and fuse with
the membrane, which permits the norepinephrine to diffuse out of the vesicle into the extracellular
space
 The norepinephrine binds to the post-synaptic receptors i.e the adrenoceptors and simulates the
effector organ response.
 NOTE: epinephrine is not the primary neurotransmitter for the sympathetic nervous system, it is the
primary hormone, norepinephrine is the primary neurotransmitter.
Norepinephrine and Epinephrine
Removal and Metabolism
 The binding of NE to its receptor depends on the concentration of NE in the vicinity of the
receptor.
 If the nerve stops releasing NE, then the NE concentration in the junctional cleft will
decrease and NE will leave the receptor
 There are several mechanisms by which the norepinephrine is removed from the
intercellular (junctional) space and therefore from the postjunctional receptor:
 1.Most (~90%) of the NE is transported back into the nerve terminal by a neuronal
reuptake transport system i.e norepinephrine autoreceptors. This transporter is blocked
by cocaine; therefore, cocaine increases junctional NE concentrations by blocking its
reuptake and subsequent metabolism. (This is a major mechanism by which cocaine
stimulates cardiac function and raises blood pressure.)
 2. Some of the junctional NE diffuses into capillaries and is carried out of the tissue by the
circulation. Therefore, high levels of sympathetic activation in the body increase the
plasma concentration of NE and its metabolites.
 3.Some of the junctional NE is metabolized within the extracellular space before reaching
the capillaries.
 4.A small amount of NE (~5%) is taken up by the postjunctional tissue (termed
"extraneuronal uptake") and metabolized.
 NE and epinephrine are metabolized by the enzymes catechol-O-
methytransferase (COMT) and monoamine oxidase (MAO). The final product of
these pathways is vanillylmandelic acid (VMA). This final product, along with
its precursors normetanephrine and metanephrine, is measured in urine and
plasma in the diagnosis of pheochromocytoma, which can cause severe
hypertension and cardiac arrhythmias.

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Adrenaline

Adrenaline ( Also known as

 Epinephrine is synthesized from norepinephrine within the adrenal medulla,

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