Catecholamines

Question 1

Describe the adrenal medulla

Answer 1

• 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

Question 2

Describe the synthesis pathway for epinephrine and norepinephrine

Answer 2

• Begins with phenylalanine
• Converted to tyrosine
• Converted to dihydroxyphenylalanine catalysed by tyrosine hydroxylase
• Then to dopamine
• Then to norepinephrine
• Then to epinephrine

Question 3

What are the sources of epinephrine in the blood?

Answer 3

Adrenal medulla only

Question 4

What are the sources of norepinephrine in the blood?

Answer 4

• Adrenal medulla

- Postganglionic sympathetic neurons

Question 5

What is the function of continual secretion of catecholamines? Use arterioles as an example

Answer 5

• 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

Question 6

Outline the kinetics of catecholamines

Answer 6

• 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

Question 7

Why can diseases of the adrenal medulla not be assessed by measuring the level of catecholamines in the blood?

Answer 7

• 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

Question 8

Compare the epinephrine and norepinephrine from the arenal medulla as opposed to the nervous system

Answer 8

• Same effect
• Lasts longer from adrenal medulla
• Highly responsive
• More generalised from adrenal medulla

Question 9

Explain the relationship between teh nervous system and the adrenal medulla

Answer 9

• 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

Question 10

Describe the adrenergic receptors

Answer 10

• 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

Question 11

Describe the effect of catecholamines binding to alpha-receptors

Answer 11

• Vasoconstriction
• Pupil dilation
• intestinal relaxation
• Pilomotor contraction
• Bladder sphincter contraction

Question 12

Describe the effect of catecholamines binding to beta-1 receptors

Answer 12

• Increased heart rate

- Increased contractility

Question 13

Describe the effect of catecholamines binding to beta-2 receptors

Answer 13

• Vasodilation
• Bronchodilation
• Glycogenolysis
• Lipolysis

Question 14

What are the clinal consequences of SNS activation?

Answer 14

• Pupil dilation
• Reduced secretions
• Sweating
• Increased metabolism
• Tachycardia
• General vasoconstriction
• Tachycardia
• Increased cardiac output
• Bronchodilation
• Decreased gastrointestinal motility
• Altered metnal state (increased alertness)

Question 15

What are the intracellular pathways for signal transduction?

Answer 15

• Adenyl cyclase
• Phospholipase C, PI3, and DAG
• Ion channels

Question 16

Describe adenyl cyclase pathway of beta-receptors

Answer 16

• Binding to cell surface protein
• Activates G-protin
• Stimulates adenylyl cyclase
• Generates cAMP
• Activates protein kinase A
• Protein phosphorylated
• Biological response initiated

Question 17

Describe the effects of cAMP

Answer 17

• 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

Question 18

Describe the effects of cAMP in the heart

Answer 18

• 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

Question 19

Describe the phospholipase C pathway of alpha adrenoceptors

Answer 19

• 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+

Question 20

What does tissue response to catecholamines vary according to?

Answer 20

• Type and density of receptors

- Relative concentrations of epinephrine and norepinephrine locally

Question 21

What is the effect on arterioles in response to catecholamines in
a. the intestines
b. the muscles
and what is the function of this?

Answer 21

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

Question 22

What are the metabolic effects of catecholamines?

Answer 22

• Increase amount of readily available energy by mobilising glucose and fatty acids
• Increase glycogenolysis
• Increase gluconeogenesis
• Hormone sensitive lipase stimulated
• TAG hydrolysed

Question 23

Why is it unusual to find normal blood glucose in cats?

Answer 23

• High stress response to sampling
• Often high glucose due to this
• Increased catechoamines leading to increased release of glucose from storage molecules

Question 24

What are the metabolic effects of catecholamines combined with in the fight or flight response?

Answer 24

• Increased heart rate and contractility
• Increased cardiac output and bblood pressure
• Shift in perfusion to increase central and reduce peripheral

Question 25

Comapre the metabolic and cardiac effects of epinephrine vs norepinephrine

Answer 25

- 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)

Question 26

Compare the actions of epinephrine and norepinephrine on the blood vessels within muscle

Answer 26

- Epinephrine acts on beta-2-receptors causing casodilation | - Noreprinephrine acts on alpha-receptros causing strong vasoconstriction (shock)

Question 27

What are the main aims fo the SNS?

Answer 27

To respond to starvation, shock and facilitate resuscitation