Noradrenaline

Question 1

What is the structural difference between adrenaline and noradrenaline?

Answer 1

Adrenaline has an extra CH3

Question 2

Where is NA released from?

Answer 2

Post-ganglionic neurones of the Sympathetic nervous system

Question 3

What enzyme converts tyrosine to DOPA?

Answer 3

Tyrosine Hydroxylase

Question 4

What enzyme converts DOPA to dopamine?

Answer 4

DOPA decarboxylase

Question 5

What enzyme converts dopamine to NA?

Answer 5

Dopamine Beta-hydroxylase

Question 6

What are dopaminergic neurones?

Answer 6

Neurones that only synthesise dopamine, they are missing the dopamine B hydroxylase enzyme (so cant make NA)

Question 7

Is NA released from a neurone end terminal or varicosity?

Answer 7

Varicosity

Question 8

Steps of NA synthesis

Answer 8

Tyrosine taken into neurone, converted to DOPA converted to dopamine (into a vesicle), then still within vesicle converted to NA

Question 9

What does the sympathetic NA target?

Answer 9

Vasculature (dilate), smooth muscles of bronchioles (dilate), eye (dilate)

Question 10

What are the effects of increased sympathetic activity to the heart?

Answer 10

Increased chronotropy and inotropy

Question 11

How is NA released? And where from?

Answer 11

Wave of depolarisation arrives at varicosity, triggers opening of Ca2+ channels, Ca2+ influx, via synaptotagmin, brings vesicle to membrane, docks onto SNARE complex, fuses with membrane and releases NA

Question 12

How is release of NA regulated?

Answer 12

Mainly by amount of sympathetic activity, ie more ACh released from pre-ganglionic neurone, more NA released from post-ganglionic

Question 13

Name different ways NA is removed from synaptic cleft?

Answer 13

Mainly= re-uptake back into neurone via NA transporter (NET). Other ways: by other cells in vicinity (extra-neuronal uptake), into circulation by capillaries, enzymatic degradation.

Question 14

Which enzymes are used in the break down of NA?

Answer 14

Mono-amine Oxidase (MAO), Catechol-O-methyl transferase (COMT)

Question 15

What metabolites can be measured in the blood/urine as a measure of NA activity?

Answer 15

Vanillylmandelic Acid (VMA), 3-Methoxy-4-Hydroxy-Phenylglycol (MHPG)

Question 16

What is Pheochromocytoma?

Answer 16

Tumour of Chromaffin cells, secretes NA, Adrenaline leading to high BP (TF damaging organs)

Question 17

What is alpha methyl tyrosine?

Answer 17

Competitive inhibitor of tyrosine hydroxylase (TF less NA synthesised as less dopamine)

Question 18

What is alpha methyl DOPA?

Answer 18

A false substrate for DOPA decarboxylase

Question 19

Is alpha methyl DOPA a competitive inhibitor?

Answer 19

No, it is a false substrate

Question 20

What are the effects when using alpha methyl DOPA?

Answer 20

Converts DOPA to methyl noradrenaline and methyl adrenaline, these cannot function as NT’s so are themselves ‘false substrates’ (TF less sympathetic tone)

Question 21

What is Guanethidine used for?

Answer 21

Used for severe hypertension, it decreases CO

Question 22

What is Guanethidine?

Answer 22

Taken up by NET/Uptake 1(?), competes with NA in neurones, is actively transported into the vesicle by VMAT, accumulates inside vesicle TF depletes the stores of NA

Question 23

How is NA synthesised?

Answer 23

From Tyrosine->DOPA->Dopamine->Noradrenaline(->Adrenaline)

Question 24

List some A adrenoceptor antagonists

Answer 24

Prazosin Doxazosin. Both treat hypertension, but can cause postural hypotension, dizziness (TF taken at night)

Question 25

List some B adrenoceptor antagonists, what they do, side effects

Answer 25

Propranolol, Atenolol (B1 & B2), Metoprolol, Bisprolol (B1). Treat hypertension, side effects include bradycardia, bronchispasms, hypoglycaemia