13. Noradrenergic neurotransmission

Question 1

What does the chemical group that monoamin neurotransmitters belong to?

Answer 1

One aminogroup derived from aromatic amino acids through decarboxylation

Question 2

What are 2 examples of monoamine neurotransmitters groups?

Answer 2

1/ Catecholamines
2/ Indolamines

Question 3

What are some examples of Catecholamines?

Answer 3

1/ noradrenaline/norepinephrine (adrenaline/epinephrine)
2/ dopamine

Question 4

What is an example of Indolamines?

Answer 4

serotonine

Question 5

What is the structure of Cathecholamines

Answer 5

cathecol (benzene diol) plus amine-containing side chain

Question 6

What are Cathecholamines synthesized from?

Answer 6

They are synthesized from tyrosine (phenylalanine)

Question 7

What are some chemical characteristics of Cathecholamines?

Answer 7

poorly absorbed and are degraded in the stomach can not cross the blood brain barrier

Question 8

Where can you find Noradrenaline - norepinephrine (neurotransmitter)?

Answer 8

– brain
- postganglionic sympathetic neurons
- small amount in the circulation as a hormon

Question 9

Where can you find Adrenaline - epinephrine (hormone)?

Answer 9

• from the adrenal medulla
• in small portion of neurons in the central nervous system

Question 10

Where can you find Dopamine (neurotransmitter)?

Answer 10

– brain modulator
– in the periphery (kidney)

Question 11

Identify this molecule

Answer 11

L-DOPA
=> 3,4-Dihydroxy-L-phenylalanine

Question 12

Identify this molecule

Answer 12

Dopamine
-> 3-4-dihydroxy-phenethylamine

Question 13

Identify this molecule

Answer 13

Noradrenaline – norepinephrine

Question 14

Identify this molecule

Answer 14

Adrenaline – epinephrine

Question 15

Tyrosine synthesis
-> Identify this molecule

Answer 15

5,6,7,8 - Tetrahydrobiopterin

Question 16

Tyrosine synthesis
-> Identify 1 & 2

Answer 16

1/ Dihydrobiopterin reductase
2/ Phenylalanine hyroxylase

Question 17

What are the consequences of tetrahydrobiopterin deficiency?

Answer 17

Dopamine
Noradrenaline
Serotonine

Question 18

Tyrosine synthesis
-> What are consequences of PAH deficiency?

Answer 18

classic PKU
1:8000-9000
phenylpyruvate, phenyllactate
phenylacetate
Therapy: diet

Question 19

What are Amino acid derivatives?
-> What is the role of Tyrosine hydroxylase?

Answer 19

Tyrosine hydroxylase can catalyse phenylalanine
➔ tyrosine conversion

Question 20

What is the enzyme involving in melanin synthesis?

Answer 20

melanocyte specific copper-dependent tyrosinase

Question 21

Noradrenergic synapse
-> What is the role of AMPT?

Answer 21

It inhibits tyrosine hydroxylase and norepinephrine synthesis

(AMPT (alpha-methyl-para-tyrosine) is an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis.)

Question 22

Noradrenergic synapse
-> What is the role of Reserpine?

Answer 22

It inhibits VMAT (Vesicular monoamine transporter) and depletes norepinephrine stores

Question 23

Noradrenergic synapse
-> What is the role of NRI?

Answer 23

Antidepressant that inhibit the norepinephrine transporter (same with SNRI)

Question 24

Noradrenergic synapse
-> What is the role of SNRI?

Answer 24

Antidepressant that inhibit the norepinephrine transporter (same with NRI)

Question 25

Noradrenergic synapse -> What is the role of Tropolone?

Answer 25

It inhibits COMT (Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines, catecholestrogens, and various drugs and substances having a catechol structure)

Question 26

Noradrenergic synapse -> What is the role of Prazosin?

Answer 26

An alpha-1 antagonist

Question 27

Noradrenergic synapse -> What is the role of MAOI?

Answer 27

An antidepressant inhibiting MAO(A) (An enzyme called monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain.)

Question 28

Noradrenergic synapse -> What is the role of Yohimbine?

Answer 28

What is an alpha 2 antagonist

Question 29

Noradrenergic synapse -> What is the role of Propranolol?

Answer 29

a Beta antagonist

Question 30

Synthesis of Dopamine

Answer 30

Question 31

Synthesis of Noradrenaline

Answer 31

Question 32

Synthesis of Adrenaline

Answer 32

Question 33

What is tyrosine hydroxylase?

Answer 33

a mixed function oxygenase (monooxygenase) Rate limiting enzyme. (Catecholamines: negative feedback) Activation by Ca2+ (Ca2+/calmodulin-dependent kinase) During increased sympathetic activity – increased tyrosine hydroxylase activity

Question 34

What is the role of L-DOPA in therapy?

Answer 34

Parkinson’s disease

Question 35

The role of Dopa-decarboxylase inhibitors?

Answer 35

L-DOPA → Parkinson’s disease

Question 36

The role of α-metil-DOPA inhibitors?

Answer 36

α-metil-DOPA → hypertension therapy (α2-receptor-agonist)

Question 37

Uptake of norepinephrine/epinephrine/dopamine into synaptic vesicles -> Characteristics of VMTA 2 (VMAT: vesicular monoamine transporter)

Answer 37

VMTA 2 (VMAT: vesicular monoamine transporter) vesicular membrane transporter 2 (-12 transmembrane domain) NE -broad substrate-specificity to E biogenic amines DA (triptamine, tiramine, amfetamin – compete with endogenous catecholamine) (-high affinity for reserpine irreversible inhibitor – depletion of vesicles) (-altered VMTA2 expression in bipolar disease (lithium influences)

Question 38

Uptake of catecholamines by presynaptic terminals

Answer 38

* Active transport * Na+ cotransport (secondary active transport) * Sustained depolarization *→ reverse function

Question 39

What are Inhibitors for Uptake of catecholamines by presynaptic terminals?

Answer 39

Cocain tricyclic antidepressant

Question 40

Relative harmfulness of drugs -> The role of cocaine?

Answer 40

inhibits noradrenaline, dopamine serotonine reuptake

Question 41

What happen during Cocaine intoxication?

Answer 41

Alpha and beta adrenerg receptor stimulation Hypertension, tachycardia, chest pain Agitated, tremulous Treatment: benzodiazepines

Question 42

Treatment for cocaine intoxication

Answer 42

benzodiazepines

Question 43

What is The mode of action of amphetamine?

Answer 43

an indirectly acting sympathomimetic amine: Non-exocytotic release of NA

Question 44

What happen during Non-exocytotic release of NA?

Answer 44

NA release, MAO – monoamine oxidase inhibitor, NET inhibitor,

Question 45

Catabolism of catecholamines -> most of the released noradrenaline recaptured by ____

Answer 45

NET (Sodium- dependent noradrenaline transporter SLC6A2) (MAO – monoamine oxidase COMT – catechol oxymethyl transferase)

Question 46

Describe Catabolism of catecholamines?

Answer 46

(MAO A) in the gastrointestinal tract and liver – prevents access of ingested indirectly acting amines (e.g. tyrosine➔tyramine) to the general circulation

Question 47

Patients on monoamine oxidase inhibitors (especially MAO-A inhibitors or non- selective MAO inhibitors) are advised to avoid ___ (what food?)

Answer 47

tyramine rich foods.

Question 48

Name of a MAO – monoamine oxidase inhibitor?

Answer 48

Cigarette smoke

Question 49

What are the 2 Enzymes in the metabolism of noradrenaline?

Answer 49

MAO – monoamine oxidase COMT – catechol oxymethyl transferase

Question 50

The role of MAO – monoamine oxidase

Answer 50

oxidative deamination of catecholamines (adrenaline, noradrenaline, dopamine, serotonine)

Question 51

The role of COMT – catechol oxymethyl transferase

Answer 51

COMT: methyl transfer to the 3-hydroxy group on the ring from S-adenosylmethionine (SAM) (adrenaline, noradrenaline, dopamine) (multiple location: brain, liver, kidney)

Question 52

What is Pheochromocytoma?

Answer 52

Most common tumor of the adrenal medulla in adults Derived from chromaffin cells Most tumors secrete epinephrine, norepinephrine, and dopamine, which can cause episodic hypertension.

Question 53

Episodic hyperadrenergic symptoms (5 P’s):

Answer 53

Pressure (high BP) Pain (headache) Perspiration Palpitations (tachycardia) Pallor

Question 54

Therapy for Pheochromocytoma

Answer 54

α antagonist (non-selective, irreversible) Surgery

Question 55

The main pathways of noradrenaline metabolism -> Identify 1 - 2

Answer 55

1/ VMA: Vanillin-mandulasav 2/ MPHG

Question 56

The main pathways of noradrenaline metabolism -> Identify 1 - 2

Answer 56

1/ NM: normetanephrine 2/ NA: noradrenaline

Question 57

The main pathways of noradrenaline metabolism -> Identify enzyme a & b

Question 58

The main pathways of noradrenaline metabolism -> Identify enzyme a & b

Answer 58

a/ AR: Aldehyde reductase b/ ADH: aldehyde dehydrogenase

Question 59

For the synthesis of dopamine, epinephrine and norepinephrine -> which reaction is the rate-limiting step?

Answer 59

The synthesis of DOPA from Tyrosine -> catalyzed by tyrosine hydroxylase

Question 60

How can step 1 be activated?

Answer 60

activation by phosphorylation: Ca2+/calmodulin-dependent kinase PKA, PKC, PKG

Question 61

The main pathways of noradrenaline metabolism -> What is the synthesis location of Dopamin

Answer 61

Cytosol

Question 62

The main pathways of noradrenaline metabolism -> What is the synthesis location of Epinephrine

Answer 62

Cytosol

Question 63

The main pathways of noradrenaline metabolism -> What is the synthesis location of Norepinephrine

Answer 63

Synaptic vesicles

Question 64

The adrenal medulla releases ___ and ____ into the bloodstream

Answer 64

epinephrine (adrenaline) and norepinephrine (noradrenaline)

Question 65

Cellular view of catecholamine synthesis. -> ____ synthesizes and stores epinephrine in a sequence of four enzymatic and three transport steps

Answer 65

The chromaffin cell

Question 66

Cellular view of catecholamine synthesis. The chromaffin cell synthesizes and stores epinephrine in a sequence of four enzymatic and three transport steps -> What are they?

Answer 66

AADC, amino acid decarboxylase; DA, dopamine; DBH, dopamine b-hydroxylase; Epi, epinephrine; NE, norepinephrine; TH, tyrosine hydroxylase.