Session 8.4: The ANS: Pharmacological Intervention in ANS - Adrenergic Transmission

Question 1

where does (nor)adrenergenic function occur

Answer 1

sympathetic - at neuroeffector junction of post ganglionic fibres -

Question 2

how is the post ganglionic sympathetic neurons specialised

Answer 2

possess a highly branched axonal network with numerous variscosities - for calcium dependent vesicular noradrenaline release (localised release)

Question 3

what occurs within a noradrenergic variscosity

Answer 3

synthesis of neurotransmitter
package neurotransmitter
vesicular release
fusion of vesicles
ACh release
effect on receptor
high affinity uptake of noradreanline into varisocity - usually repackaged and reused or some metabolism

Question 4

how is noradrenaline synthesised

Answer 4

tyrosine accumulates in variscosity -> DOPA by tyrosine hydroxylase -> Dopamine by DOPA decarboxylase -> into vesicle which contains dopamine beta-hydroxylase which converts dopamine into noradrenaline

Question 5

why does adrenaline instead of noradrenaline accumulate in chromaffin cells

Answer 5

within adrenal medulla noradrenaline is converted to adrenaline by phenylethanolamine N-methyltransferase, so adrenaline release into bloodstream and acts as sympathetic hormone

Question 6

how is noradrenaline released

Answer 6

by calcium dependent exocytosis:

1. varicosity depolarises
2. opens voltage gated calcium channels
3. calcium enters
4. causes vesicles to fuse with membrane to release contents into cleft
5. noradrenaline interacts with adrenoreceptors in post synaptic memrbane to initiate signalling in effector tissue

Question 7

where else does noradrenaline interact and why is this

Answer 7

interacts with pre-synaptic adrenoreceptors to regulate processes within nerve terminal so how much noradrenaline is released

Question 8

how is noradrenaline removed

Answer 8

by noradrenaline transporter proteins - small time to influence both pre and post-synaptic adrenoreceptors

Question 9

how are noradrenaline actions terminated (taken up by varicosity)

Answer 9

by re uptake into pre synaptic terminal by sodium dependent, high affinity transporter = uptake 1 (NET)
any noradrenaline not recaptured by uptake 1 is taken up by low affinity, non-neuronal mechanism = uptake 2

Question 10

how can adrenaline be repackaged for use after being terminated

Answer 10

Metabolism - within pre synaptic terminal any noradrenaline not taken up by vesicles can be metabolised by monoamine oxidase or catechol-O-methyltransferase

Question 11

how are adrenoreceptor agonist and antagonist used clinically

Answer 11

beta 2 adrenoreceptor selective agonists (eg: salbutamol) - reverses/opposes bronchoconstriction - ashma
limits CV effects by using beta adrenoreceptor agonist as if non selective can not differentiate between CV and respiratory effects
alpha 1 adrenoreceptor selective antagonists (doxazosin) and beta 1 adrenoreceptor selective antagonists (atenolol) to treat CV disorders such as hypertension