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Fundamentals of Neuroscience Semester 2 > Noradrenaline Synthesis, Release and Degradation > Flashcards

Noradrenaline Synthesis, Release and Degradation Flashcards

1
Q

Why is autonomic pharmacology important?

A
  • ANS innervates most viscera (organs)
  • Unlike CNS, not protected by blood-brain barrier so. is exposed to many chemical compounds
  • widespread therapeutic use
  • important toxicology
  • similar methods and mechanisms of transmission in multiple different tissues
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2
Q

What is the autonomic nervous system?

A
  • part of the peripheral nervous system that conveys all outputs from the CNS to the rest of the body, except the motor innervation of skeletal muscle
  • largely outside voluntary control
  • 3 divisions: sympathetic, parasympathetic and enteric (intrinsic system within the wall of the gut)
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3
Q

What processes does the autonomic system regulate?

A
  • smooth muscle tone
  • all exocrine secretions
  • some endocrine secretions
  • heart rate and force
  • certain metabolic porcesses
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4
Q

What’s the difference between endocrine and exocrine?

A
  • endocrine glands secrete hormones directly into the blood

- exocrine glands secretes its product into ducts that lead to the target tissue

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5
Q

What is the sympathetic action on the iris?

A

pupil dilation

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6
Q

What is the sympathetic action on the salivary glands?

A

increase salivation

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7
Q

What is the sympathetic action on the oral/nasal mucosa?

A

reduce mucus

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8
Q

What is the sympathetic action on the heart?

A

increase rate and force

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9
Q

What is the sympathetic action on the lung?

A

dilate bronchial muscle

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10
Q

What is the sympathetic action on the gut?

A

reduce motility, increase sphincter tone

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11
Q

What is the sympathetic action on the liver?

A

convert glycogen to glucose

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12
Q

What is the sympathetic action on the adrenal medulla?

A

secrete adrenaline

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13
Q

What is the sympathetic action on the bladder?

A

wall relaxed, sphincter closed

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14
Q

How do you synthesise noradrenaline and adrenaline?

A
  1. Tyrosine is converted to dihydroxyphenylalanine (DOPA) using tyrosine hydroxyls
  2. DOPA is converted to dopamine using DOPA decarboxylase
  3. Dopamine is converted to noradrenaline using dopamine-beta-hydroxylase
  4. noradrenaline is converted into adrenaline using phenylethanolamine N-methyl transferase
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15
Q

What is the rate limiting step in the production of adrenaline?

A

tyrosine hydroxyls

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16
Q

What uses feedback inhibition on tyrosine hydroxyls?

A

NAd

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17
Q

If you want info on inhibitors for these reactions

A

look on slides

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18
Q

What is Ad and NAd stored in?

A

chromaffin granules (found in neurotransmitter vesicles within the adrenal gland and the nerve terminals)

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19
Q

What is the main enzyme that packages NAd or dopamine into the vesicles?

A

VMAT

20
Q

How does VMAT work?

A

-using the electrochemical gradient of H+ to move dopamine into the vesicles (H+ grad maintained by a pump)

21
Q

What happens once the dopamine is inside the vesicles?

A

can be converted into noradrenaline. by dopamine dehydroxylase

22
Q

Can VMAT transport noradrenaline into the vesicle?

A

yes

23
Q

What inhibits the VMAT transporter?

A

reserpine

24
Q

Whats the PH like inside the vesicle?

A

low (so H+ moves out as dopamine moves in)

25
Q

Why is reserpine not used today?

A

too many side effects

26
Q

Describe how exocytosis from sympathetic nerves works

A
  1. arrival of action potential causes depolarisation of varicosity
  2. Ca2+ entry causes an increase in the conc of free Ca2+ in the varicosity
  3. This activates Ca2+ sensitive proteins that initiate the process of expocytosis
27
Q

How is the release of neurotransmitter regulated?

A
  • sympathetic nerve terminals contain many different receptors for different substances
  • a variety of substances can act on the receptors to regulate release either by facilitating or inhibiting release
28
Q

What can happen once noradrenaline is released?

A

can act locally on presynaptic receptors to inhibit its own release and the release of ATP using α2-adrenoceptors

29
Q

What other factors can regulate the release of noradrenaline?

A
  • ACh-inhibits release via muscarinic receptors
  • Adenosine-inhibits
  • Opiods- inhibit release
  • Angiotensin II- facilitates release
30
Q

What are the two ways of catecholamine uptake?

A

-neuronal
-non-neuronal
(both active transport mechanisms)

31
Q

How is catecholamines taken up neuronally?

A
  • second active transporter NAT

- cotransports Na+, Cl- and catecholamine

32
Q

What is the main mechanism for terminating the actions of NAd?

A

NAT

33
Q

What is NAT inhibited by?

A
  • cocaine
  • tricyclic antidepressants
  • phenolxybezamine
34
Q

What is cocaine an inhibitor of?

A

-catecholamine transporters, DAT, SERT and NAT

35
Q

How does non-neuronal uptake occur?

A

taken up by cardiac & smooth muscle and endothelium

36
Q

What are the two main intracellular enzymes used in the metabolic breakdown of catecholamines?

A
  • monoamine oxidase (MAO)

- catechol-o-methyl transferase (COMT)

37
Q

Where is MAO found?

A

in many tissues including nerve terminals bound to the mitochondria

38
Q

What does MAO convert catecholamines into?

A

aldehydes

39
Q

What happens to the aldehydes?

A

metabolised by aldehyde dehydrogenase or aldehyde reductase

40
Q

What are MAO inhibitors used for, clinically?

A

anti-depressents

41
Q

How does COMT work?

A

-converst catecholamines to methoxy derivatives by transferring a methyl group to one of the catechol OH groups

42
Q

Whats the main final metabolite of Ad and NAd?

A

VMA

43
Q

What are noradrenergic neurone blocking drugs?

A

inhibit noradrenaline release from sympathetic nerve terminals

44
Q

What are some examples of indirectly acting sympathetic amines?

A
  • amphetamine
  • ephedrine
  • tyramine
45
Q

How does amphetamine work?

A
  • structurally related to noradrenaline
  • transported into NAT and into vesicles
  • displaces noradrenaline which leaks out via NAT
  • similar effect on dopamine
  • effect is long-lasting

Fundamentals of Neuroscience Semester 2 (10 decks)

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