Catecholamines Flashcards
Which nervous system uses catecholamines?
The sympathetic
Describe the normal neurone structure of nerves in the sympathetic and then compare to the neurons of the adrenal medulla
Normal= short pre ganglionic and long post Adrenal= long pre ganglionic and short post
Describe the difference between the tumours of the adrenal cortex and adrenal medulla
- Diseases of the medulla are less common
- Can get tumours of the medulla= they are functional and produce excess catecholamines
What is the rate limiting step in the synthesis of catecholamines?
-The enzyme tyrosine hydroxylase
Where does circulating epinephrine and nor epinephrine come from?
- ALL epinephrine in the blood is from the adrenal medulla
- Norepinephrine comes from 2 sources
1) adrenal medulla
2) postganglionic sympathetic neurons
How is vascular tone maintained?
- Basal sympathetic tone
- It is accomplished by the resting secretion from adrenal medulla
Describe the kinetics of catecholamines
- Stored in secretory vesicles
- Released via exocytosis
- Circulate freely in the blood
- Metabolised by liver and kidneys
- Very short plasma half life (not very stable)
- Unmetabolised epinephrine/ norepinephrine is excreted in the urine
What stimulates release of adrenaline and noradrenaline from the adrenal medulla?
- Action potential from the pre ganglionic fibre secretes dopamine which causes an influx of Ca
- Stimulates more catecholamines to be produced and the exocytosis of the secretory vesicles resulting in epinephrine and norepinephrine entering the blood.
List adrenergic receptors
-A/B adrenergic receptors
What are the effects of catecholamines binding to alpha receptors?
- Vasoconstriction
- Pupil dilation
- Intestinal relaxation
- Pilomotor contraction
- Bladder sphincter contraction
What are the effects of catecholamines binding to B1 and B2 receptors?
B1= increases heart rate and contractility B2= vasodilation, bronchodilation, glycogenolysis and lipolysis
Which receptor is found on the cardiac myocytes?
B1
List some of the consequence of SNS activation
- Dilated pupils
- Sweating
- Tachycardia
- General vasoconstriction
- Increased cardiac output
- Bronchodilation
Describe the signal transduction of catecholamines
-Binds to receptors and activates second messengers- often G coupled
Which adrenergic receptors use adenyl cyclase?
B receptors
remember adenyl cyclase-> cAMP-> activates pkA-> protein is phosphorylated and response occurs
What are the effects of cAMP?
- Subunit of pkA enters nucleus
- Binds to CREB and phosphorylates
- CREB-P binds to CRE and changes gene expression
Explain the impact of phospholipase C at alpha receptors
- Hormone binds to cell receptor
- Phospholipase C activated via a G protein
- PIP2 is broken down to IP3 and DAG
- DAG activated membrane bound protein kinase C
- Protein is phosphorylated
- Biological response resulting in increased intracellular Ca
Which receptor does albuterol act on and what are its affects?
Beta 2
Stimulates adenyl cyclase -> increased cAMP results in dilation of bronchiole smooth muscle
Which receptor does dobutamine work on and what are its effects?
B1
What receptor does atenolol work on and what are its effects?
Blocks B1
Decreases blood pressure and slows heart rate
Why are the different receptors important in the sympathetic nervous system?
- Allow catecholamines to produce different effects in different tissues to help with fight/ flight
e. g. reduces blood flow to intestines whereas increases blood flow to muscle
What are the metabolic effects of catecholamines?
- Increase glycogenolysis
- Stimulate gluconeogenesis
- Stimulates HSL (hormone sensitive lipase) -> increases circulating plasma fatty acid levels used to beta oxidation in mitochondria.
Describe the differences between epinephrine and norepinephrine
- Norepinephrine has greater impact on blood vessels: increases total peripheral resistance and raises blood pressure
- Epinephrine has more profound effect on the heart: increases heart rate and contractility and raises cardiac output
