Nor epinephrine and Epinephrine

seminar presentation

Presenter: Yohanes sime

moderator: Mr.Gutema (Bsc, Msc)

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 Objectives of the presentation
 To understand:-

 The synthesis/degradation and distribution of nor epinephrine

and epinephrine
 Their receptors and clinical relevance

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 Outlines of presentation
 Synthesis/degradation
 Receptors
 Distribution
 Clinical relevance

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 -

Nor epinephrine and Epinephrine

Noradrenergic system and adrenergic system

Act on adrenergic receptors

Implicated in diverse functions: mood, overall arousal, sexual

behavior, regulation of blood pressure
Epinephrine ( adrenaline)

 Plays a critical part in the body’s response to stress

 Has major effects on the peripheral NS

 limited role as a central neurotransmitter

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 Synthesis and Degradation
 Tyrosine (tyrosine hydroxylase) Dopa
Dopa decarboxylase
DA  (DA -hydroxylase) NE
In Epinephrine releasing neurons
NE  (PNMT) Epinephrine
In Nor epinephrine-releasing neurons
Reuptake into presynaptic terminal and
Metabolism by MAO and COMT

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  Tyrosine is obtained from dietary protein and is transported
from the blood into the brain.
 Each step in the formation of NE/E depends on a specific
enzyme that acts as a catalyst (an agent that increases the rate
of a chemical reaction) for that step.
 Tyrosine hydroxylase is the rate limiting enzyme in the
pathway because it determines the overall rate of the DA and
NE.

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 The level of catecholamine's within the nerve terminal, e.g.,
high catecholamine levels within the nerve terminal tend to
inhibit tyrosine hydroxylase, serving as a negative feedback
mechanism.

The rate of cell firing, e.g., when neurons are activated and
firing at a high rate, such as during stress, tyrosine hydroxylase
would be stimulated.

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 .

Tyrosine Dopa DA

tyrosine DOPA decarboxylase

hydroxylase

DA -hydroxylase

PNMT (Phenyl ethanolamine N-methyl transferase)

Norepinephrine
epinephrine

COMT/MAO

Degradation
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 .

Deactivation is accomplished by one of three methods:

(1) NE may be destroyed directly while in the synaptic cleft by

catechol-0-methyltransferase (COMT),

(2) NE may be transported back into the presynaptic terminal

where it can be stored simply for future use, or

(3) Once transported back into the presynaptic terminal, NE may

be broken down by monoamine oxidase (MAO).

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 -

Receptors
-adrenergic receptors
1 Subtypes: 1A, 1B and 1D
2 Subtypes: 2A, 2B and 2C
Inhibit the formation of cAMP
-adrenergic receptors
1, 2, 3
Stimulate the formation of cAMP
3 receptors recently correlated with energy
metabolism
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 .

 Found in many peripheral organ systems and in sympathetic NS

 All receptors are of the G-protein-linked type

 The Beta -1 receptor appears to be most sensitive to nor

epinephrine within the CNS

 Alpha-2 receptors also are found presynaptically, both in the

brain and in the sympathetic nervous system.
 they serve as auto receptors, regulating the release of NE from the
presynaptic terminals

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 .

Distribution
Nor epinephrine is more abundant in the CNS

1. Major cell bodies project from the locus ceruleus in the Pons -
through the medial forebrain bundle(MFB) to
– The hypothalamus, thalamus,

– Limbic structures (including the hippocampal formation, septal nuclei,

amygdala, and cingulate gyrus),

– The cerebral cortex

– Some fibers enter- the cord, the cerebellum, the brain stem

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 -

Distribution of nor epinephrine in the CNS.

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Other sources
.

2. The postganglionic neurons of the sympathetic nervous system-

(T1-L3) under the control of the hypothalamus -prepare the
body to take either aggressive or defensive action in response to
threat or stress
3. The adrenal medulla
 the primary source of epinephrine (and nor epinephrine is also
synthesized)
 released directly into the blood -act like hormones rather than
neurotransmitters
 can effect a sympathetic response

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Autonomic Responses Associated with Nor epinephrine and Acetylcholine

Organ System Sympathetic Response Parasympathetic Response

Eyes Dilates pupil Constricts pupil

Lungs Dilates bronchioles Constricts Bronchioles
Heart Increases heart rate Decreases heart rate
Increases contractility Decreases contractility
Blood Vessels
(Surface) Constricts
(Striated muscle) Dilates
(Blood pressure) Increases

Energy Increases glycogenolysis

Systems Increases release of stored glucagon,
Increases lipolysis

Gastrointestinal Inhibits GI processes Promotes GI processes

GI/GU Sphincters Constricts Relaxes
Skin Sweating
15 Piloerection
 Clinical and Drug Effects Associated with
Noradrenergic Mechanisms

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 .

Thought to play a significant role in

• arousal
• attention/vigilance
• affect
• stress/threat and memory
Anxiety-Related Disorders.
 adrenergic response of the peripheral sympathetic nervous system
(i.e., “fright–flight–fight”)
 It is believed that “central” adrenergic responses likely serve related
goal.

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 Noradrenergic systems in the brain
 Respond to perceived threats or stress,
 involved in maintaining vigilance (i.e., an increased state
of “arousal”) against potential or imminent threats.
 being “on guard” both psychologically and physiologically

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In anxiety disorders sympathetic like arousal occurs either
(1) in the absence of a real or impending threat(“Uncued” Panic attacks or
generalized anxiety disorders)
(2) to inappropriate stimuli(Cued” Panic attacks- e.g., panic disorder with
agoraphobia)
(3) continues to occur even when the threat is passed(Posttraumatic stress
disorders -PTSD)
Most associated with an increased sensitization and/or
responsivity of the locus ceruleus or the central noradrenergic
system

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 .

Adrenergic Drug Effects and Anxiety-Related Disorders

Anxiety is related to an excess of NE ??
Yohimbine is an alpha-2 antagonist-
 has anxiogenic effect
Drugs such as alcohol, morphine, or the BZDs
 exert an inhibitory influence on NE -do have anxiolytic
properties
Propranolol beta blocker
 proven quite useful for “social anxiety states-
 but not for panic disorders, GAD, or PTSD

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 .

Chronic anxiety-related disorders are more likely than not to respond

positively to various antidepressant medications
 Antidepressant(TCA, MAOI, SSRI, venlafaxine, mirtazapine)

have varying degrees of adrenergic activity in that they block the

reuptake and/or destruction of NE
 should not blocking the reuptake or destruction of NE then lead

to greater not less anxiety?

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  In the case of the antidepressants (and their capacity to inhibit

reuptake of NE),
 the effects of the excess NE on the somatodendritic and/or terminal

auto receptors of the adrenergic neurons of the locus ceruleus

(thereby limiting their firing and/or release of NE) may override any
anxiogenic effects they may have at the postsynaptic terminals

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 reference
 Clinical neuro anatomy, A neuro behavioral approach : John
E, Mendoza . Anne L foundasa

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