Noradrenaline Flashcards
Where is noradrenaline used in the autonomic nervous system
At sympathetic neuroeffector junctions, except at thermoregulatory sweat glands and arrector pili muscles
What determines whether a synaptic terminal is dopaminergic or noradrenergic?
The presence of dopamine beta-hydroxylase which converts dopamine to noradrenaline.
How is noradrenaline packaged for release?
Uptake into vesicles by VMAT
pH of vesicles is lowered by V-ATPase
Describe how the activation of beta-1 receptors in the SAN affects heart rate.
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.
Describe how activation of beta-1 receptors in the ventricles of the heart affects force of contraction.
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.
Give each adrenoceptor subtype and the g-protein that it is coupled to.
alpha 1 - Gq
alpha 2 - Gi
beta 1/2 - Gs
How is the action of noradrenaline terminated at a synapse.
Re-uptake into the neuron by uptake 1/uptake 2
Uptake into a vesicle by VMAT
Degradation by COMT/MAO/PNMT
What product of metabolism of noradrenaline can be found in the urine, and what is it used to indicate?
VMA is the final product of metabolism, used as a direct index of sympathetic activity.
What adrenoceptor subtypes are found in the liver and what are their function?
Alpha-1 and beta-2
Increase glycogenolysis
What adrenoceptor subtypes are found in vascular smooth muscle and what are their function?
alpha-2 causes vasoconstriction (vasodilation with pharmacological concentrations of adrenaline)
beta-2 causes vasodilation
What adrenoceptor subtypes are found in airway smooth muscle and what are their function?
beta-2 causing dilation
What adrenoceptor subtypes are found in GI smooth muscle and what are their function?
alpha-1 contracts sphincters
beta-2 decreases motility
What adrenoceptor subtypes are found in bladder smooth muscle and what are their function?
beta-3 contracts sphincter
What adrenoceptor subtypes are found in the SAN and what are their function?
beta-1 to increase heart rate
What adrenoceptor subtypes are found in the ventricles of the heart and what are their function?
Beta-2 to increase contractility and automaticity
What adrenoceptor subtypes are found in adipose tissue and what are their function?
Beta-1 and beta-3 to increase lipolysis
What adrenoceptor subtypes are found in skeletal muscle and what are their function?
beta-2 increase contraction speed and glycogenolysis
What adrenoceptor subtypes are found in the iris and what are their function?
alpha-1 dilate the iris
Describe the target of salbutamol and its use
Beta-2 agonist
Reduces bronchoconstriction is asthmatics
Describe the target of phenylephrine and its use
alpha-1 agonist
Aids nasal decongestion
Describe the target of clonidine and its use
alpha-2 agonist
Prolong the action of local anaesthetics
Describe the target of prazosin and its use
alpha antagonist
Treats hypertension/anxiety/PTSD
Describe the action of alpha-methyltyrosine and what it is used to treat.
Antihypertensive
Inhibits tyrosine hydroxylase, affecting the rate limiting step in conversion of tyrosine to catecholamines, decreasing the synthesis of noradrenaline.
Describe the action of alpha-methyl DOPA and what is it used to treat.
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.
Describe short term downregulation of beta adrenoceptors
BARK/GRK activated by PKA which phosphorylate the receptor, preventing activation (uncoupled)
Describe long term desensitisation of beta adrenoceptors.
Degradation of the receptor itself
Reduced receptor synthesis due to reduced mRNA production.
