Session 6+7 - Noradrenaline Flashcards
Where is Noradrenaline released in the body?
In the post ganglionic neurones of the sympathetic nervous system
Are there any post ganglionic synapses in which noradrenaline is not the transmitter?
Sweat glands
- ACh (nicotinic receptors)
Ejaculation
What are the “biogenic amines”? What is the synthetic pathway?
Biological compounds containing NH2 synthesized from tyrosine
Tryosine –> (tryosine hydroxylase) DOPA –> (DOPA decarboxylase) Dopamine –> (dopamine b-hydroxylase) Noradrenaline
Where does the synthetic production of biogenic amines take place?
The sympathetic nerve axon
Tryosine –> DOPA –> Dopamine in cytoplasm
Dopamine - Noradrenaline in synaptic vesicle
What determines whether a nerve terminal is dopaminergic or noadrenergic?
The presence of DBH, which converts dopamine to noradrenaline
How is noradrenaline packaged for release?
Packaged into synaptic vesicles, which actively take up noradrenaline via vesicular catecholamine pump
Outline the key events of post-ganglionic sympathetic innervation of target tissues
- Actions potential travels down axon and reaches pre-synaptic knob
- Voltage gates calcium ion channels open and Calcium flows in
- Calcium binds to synaptotagmin
- Vesicle containing noradrenaline brought close to membrane
- Snare complex makes a fusion pore
- Noradrenaline is released into synaptic cleft
- Binds to adrenergic receptors
- Causes influx of Na+ ions into effector organ
- Action potential generated in effector organ
List five sites of sympathetic innervation
The heart Skeletal muscle Smooth muscles Adipose tissue Glands (not sweat glands)
What is positive chronotrophy in heart rate?
Increase in HR
What is positive intropy in the heart?
Increase in force of contraction
Explain the anatomical basis for positive chronotrophy due to NA
- Right sympathetic nerve acts on the B1 adrenoreceptors of the SA node
- B1 adreno receptors activate adenylyl cylcase
- Causes increase in rate of AP generation
Explain the anatomical basis for positive inotrophy due to NA
NA acts on B1 receptors, increase in Ca2+ influx in ventricular cardiomyocyte.
For each receptor subtype, give the G protein, effector and whether in activates or inhibits
a1
Gq
Activates phospholipase C, producing secondary messenger IP3. IP3 interacts with IP3 sensitive calcium channels in sarcoplasmic reticulum
For each receptor subtype, give the G protein, effector and whether in activates or inhibits
a2
Gi
Inhibits adenylyl cyclase
Inhibits calcium channels, activates potassium channels
For each receptor subtype, give the G protein, effector and whether in activates or inhibits
B1 + B2
Gs
Stimulate adenylyl cyclase causing increase cAMP
Causes opening of calcium channels
B1 - in heart increase in force and rate of contraction
B2 In smooth muscle, causes relaxation
How are extracellular noradrenaline levells decreased?
- Noradrenaline can be taken up by noradrenaline transporter and repackaged into vesicles in presynaptic neuron
- Norepinephrine transporter
Na+ Cl- dependent reuptake
Uses Na+ gradient to move into cells - Vesicular Monoamine Transporter
Repackage into vesicles
Uses proton gradient
Name two enzymes which degrade noradrenaline
Monoamine oxidase
Catechol-O-methyltransferase
What do enzymes degrade NA into?
Its aldehyde derivative by O-methylation which can be excreted in the urine
Which products of metabolism can be measured in the blood or urine as an indirect index of sympathetic activity?
VMA and MHPG are metabolites of noradrenaline
Can be measured in urin
High levels indicative of adrean or sympathetic nervous system tumour
What are the adrenoreceptors and physiological response of liver cells?
A1, B2
Increased glycogenolysis, increased gluconeogenesis
What are the adrenoreceptors and physiological response of vascular smooth muscles?
a1 - constrict
a2 - constrict/dilate
b2 - dilate
What are the adrenoreceptors and physiological response of airways (bronchi)
a1 - constrict
b2 - dilate
What are the adrenoreceptors and physiological response of GI tract
a1 - relax
a2 - relax
b3 - relax
What are the adrenoreceptors and physiological response of the SA node of the heart
B1 - increased heart rate
