Catecholamines Flashcards
Describe the adrenal medulla
- Only makes up 10-20% of the gland
- Neuroendocrine tissue
- Acts as sympatehtic ganglion
- Embyrologically from autonomic nervous system, neural crest cell origin
- Secretes catecholamines
- Axons extend into cortex
Describe the synthesis pathway for epinephrine and norepinephrine
- Begins with phenylalanine
- Converted to tyrosine
- Converted to dihydroxyphenylalanine catalysed by tyrosine hydroxylase
- Then to dopamine
- Then to norepinephrine
- Then to epinephrine
What are the sources of epinephrine in the blood?
Adrenal medulla only
What are the sources of norepinephrine in the blood?
- Adrenal medulla
- Postganglionic sympathetic neurons
What is the function of continual secretion of catecholamines? Use arterioles as an example
- Basal rates of activity = sympathetic tone
- E.g. arterioles: sympathetic tone keeps arterioles constricted to 50% of diamete
- Increase in stimulation leads to more constriction, while decrease leads to less constriction
- Allows one system to cause both constriction and dilation
- Careful modulation using one system
Outline the kinetics of catecholamines
- Stored in secretory vesicles and released via exocytosis
- Circulate freely in blood
- Metabolised in liver and kidney, short palsma half life (1-3 mins)
- Urinary exretion of unmetabolised epinephrine and norepinephrine
Why can diseases of the adrenal medulla not be assessed by measuring the level of catecholamines in the blood?
- Constantly excreted and metabolised by liver and kidneys
- large bursts in sympathetic activity quickly removed
- Can use breakdown products to give indication of pathology in gland
- Some factors may be indicative of medullary tumours
Compare the epinephrine and norepinephrine from the arenal medulla as opposed to the nervous system
- Same effect
- Lasts longer from adrenal medulla
- Highly responsive
- More generalised from adrenal medulla
Explain the relationship between teh nervous system and the adrenal medulla
- SNS activated when rapid and large response to stimulus required
- Pre-ganglionic sympathetic neurones carry action potential to adrenal medulla, stimulate release of catecholamines (via Ach) = large output
- Adrenal medulla is equivalent to post-ganglionic sympathetic neurone
Describe the adrenergic receptors
- alpha and beta
- Alpha 1, 2
- Beta 1, 2, 3,
- Effector cells can be stimulated or inhibited
- Different receptors on different cells, thus having different effect
- Some cells have more than one type, others only one type
- Allows close modulation of cellular activity
- e.g cardiomyocytes only have beta-receptors
Describe the effect of catecholamines binding to alpha-receptors
- Vasoconstriction
- Pupil dilation
- intestinal relaxation
- Pilomotor contraction
- Bladder sphincter contraction
Describe the effect of catecholamines binding to beta-1 receptors
- Increased heart rate
- Increased contractility
Describe the effect of catecholamines binding to beta-2 receptors
- Vasodilation
- Bronchodilation
- Glycogenolysis
- Lipolysis
What are the clinal consequences of SNS activation?
- Pupil dilation
- Reduced secretions
- Sweating
- Increased metabolism
- Tachycardia
- General vasoconstriction
- Tachycardia
- Increased cardiac output
- Bronchodilation
- Decreased gastrointestinal motility
- Altered metnal state (increased alertness)
What are the intracellular pathways for signal transduction?
- Adenyl cyclase
- Phospholipase C, PI3, and DAG
- Ion channels
Describe adenyl cyclase pathway of beta-receptors
- Binding to cell surface protein
- Activates G-protin
- Stimulates adenylyl cyclase
- Generates cAMP
- Activates protein kinase A
- Protein phosphorylated
- Biological response initiated
Describe the effects of cAMP
- Catalytic subunit of protein kinase A enters nucleus
- Binds to cAMP response element binding protein (CREB) and phosphorylates
- CREB-P binds to CRE and changes genes expression
Describe the effects of cAMP in the heart
- Ca2+ channel opening time prolonged
- Strengthens contractions and increases uptake into SR at end of contraction (shortening contraction)
- Leads to stronger and more frequent contractions
Describe the phospholipase C pathway of alpha adrenoceptors
- Hormone binds to cell surface receptor
- Activates phospholipase C via G protein
- Phospholipid PIP2 broekn down to IP3 and DAG
- DAG activates membrane bound protein kinase C
- Protein phosphorylated
- Biological response is increased intracellular Ca2+
What does tissue response to catecholamines vary according to?
- Type and density of receptors
- Relative concentrations of epinephrine and norepinephrine locally
What is the effect on arterioles in response to catecholamines in
a. the intestines
b. the muscles
and what is the function of this?
Intestine: Alpha-receptor stimulates mooth myocytes of blod vessels leading to vasoconstriction
- Muscles: Beta-2 receptors, inhibits smooth myocytes of blood vessels leading to vasodilation
- Function of redistribution of blood to where it is needed for fight or flight
What are the metabolic effects of catecholamines?
- Increase amount of readily available energy by mobilising glucose and fatty acids
- Increase glycogenolysis
- Increase gluconeogenesis
- Hormone sensitive lipase stimulated
- TAG hydrolysed
Why is it unusual to find normal blood glucose in cats?
- High stress response to sampling
- Often high glucose due to this
- Increased catechoamines leading to increased release of glucose from storage molecules
What are the metabolic effects of catecholamines combined with in the fight or flight response?
- Increased heart rate and contractility
- Increased cardiac output and bblood pressure
- Shift in perfusion to increase central and reduce peripheral
Comapre the metabolic and cardiac effects of epinephrine vs norepinephrine
- Epinephrine has 5-10x greater metabolic effect than norepinephrine
- Epinephrine has greater effect on beta-receptors (and thus cardiac stimulation)
- Norepinephrine has more profound effect on blood vessels (increases total periphearl resistance and raises blood pressure)
Compare the actions of epinephrine and norepinephrine on the blood vessels within muscle
- Epinephrine acts on beta-2-receptors causing casodilation
- Noreprinephrine acts on alpha-receptros causing strong vasoconstriction (shock)
What are the main aims fo the SNS?
To respond to starvation, shock and facilitate resuscitation
