Noradrenaline

Question 1

Where is noradrenaline used in the autonomic nervous system

Answer 1

At sympathetic neuroeffector junctions, except at thermoregulatory sweat glands and arrector pili muscles

Question 2

What determines whether a synaptic terminal is dopaminergic or noradrenergic?

Answer 2

The presence of dopamine beta-hydroxylase which converts dopamine to noradrenaline.

Question 3

How is noradrenaline packaged for release?

Answer 3

Uptake into vesicles by VMAT

pH of vesicles is lowered by V-ATPase

Question 4

Describe how the activation of beta-1 receptors in the SAN affects heart rate.

Answer 4

They are Gs coupled, so increase cAMP in the cells. This increases HCN channel function, shortening the time of the funny current and therefore increasing the rate of firing of action potentials, which increases the rate of contractions.

Question 5

Describe how activation of beta-1 receptors in the ventricles of the heart affects force of contraction.

Answer 5

Gs coupled so increase cAMP in the cells, which activates PKA
This has a number of effects:
- Increases calcium uptake into the cell
- Increases calcium uptake into the SR
- Increases calcium release from the SR
- Increases sensitivity of contractile apparatus
All together these increase the force of contraction.

Question 6

Give each adrenoceptor subtype and the g-protein that it is coupled to.

Answer 6

alpha 1 - Gq
alpha 2 - Gi
beta 1/2 - Gs

Question 7

How is the action of noradrenaline terminated at a synapse.

Answer 7

Re-uptake into the neuron by uptake 1/uptake 2
Uptake into a vesicle by VMAT
Degradation by COMT/MAO/PNMT

Question 8

What product of metabolism of noradrenaline can be found in the urine, and what is it used to indicate?

Answer 8

VMA is the final product of metabolism, used as a direct index of sympathetic activity.

Question 9

What adrenoceptor subtypes are found in the liver and what are their function?

Answer 9

Alpha-1 and beta-2

Increase glycogenolysis

Question 10

What adrenoceptor subtypes are found in vascular smooth muscle and what are their function?

Answer 10

alpha-2 causes vasoconstriction (vasodilation with pharmacological concentrations of adrenaline)
beta-2 causes vasodilation

Question 11

What adrenoceptor subtypes are found in airway smooth muscle and what are their function?

Answer 11

beta-2 causing dilation

Question 12

What adrenoceptor subtypes are found in GI smooth muscle and what are their function?

Answer 12

alpha-1 contracts sphincters

beta-2 decreases motility

Question 13

What adrenoceptor subtypes are found in bladder smooth muscle and what are their function?

Answer 13

beta-3 contracts sphincter

Question 14

What adrenoceptor subtypes are found in the SAN and what are their function?

Answer 14

beta-1 to increase heart rate

Question 15

What adrenoceptor subtypes are found in the ventricles of the heart and what are their function?

Answer 15

Beta-2 to increase contractility and automaticity

Question 16

What adrenoceptor subtypes are found in adipose tissue and what are their function?

Answer 16

Beta-1 and beta-3 to increase lipolysis

Question 17

What adrenoceptor subtypes are found in skeletal muscle and what are their function?

Answer 17

beta-2 increase contraction speed and glycogenolysis

Question 18

What adrenoceptor subtypes are found in the iris and what are their function?

Answer 18

alpha-1 dilate the iris

Question 19

Describe the target of salbutamol and its use

Answer 19

Beta-2 agonist

Reduces bronchoconstriction is asthmatics

Question 20

Describe the target of phenylephrine and its use

Answer 20

alpha-1 agonist

Aids nasal decongestion

Question 21

Describe the target of clonidine and its use

Answer 21

alpha-2 agonist

Prolong the action of local anaesthetics

Question 22

Describe the target of prazosin and its use

Answer 22

alpha antagonist

Treats hypertension/anxiety/PTSD

Question 23

Describe the action of alpha-methyltyrosine and what it is used to treat.

Answer 23

Antihypertensive
Inhibits tyrosine hydroxylase, affecting the rate limiting step in conversion of tyrosine to catecholamines, decreasing the synthesis of noradrenaline.

Question 24

Describe the action of alpha-methyl DOPA and what is it used to treat.

Answer 24

Antihypertensive
Competitive inhibitor of DOPA decarboxylase, decreasing noradrenaline production.
Also can be converted to alpha-methyl noradrenaline which is an alpha-2 agonist in the CNS, reducing sympathetic output.

Question 25

Describe short term downregulation of beta adrenoceptors

Answer 25

BARK/GRK activated by PKA which phosphorylate the receptor, preventing activation (uncoupled)

Question 26

Describe long term desensitisation of beta adrenoceptors.

Answer 26

Degradation of the receptor itself

Reduced receptor synthesis due to reduced mRNA production.