Catecholamines Flashcards
Catecholamines lecture 15/1/2021 (ENI). There is a useful table of therapeutics and receptors on Page 4.
What are the two broad regions of the adrenal glands?
Cortex - secretes steroid hormones (e.g. aldosterone, cortisol)
Medulla - secretes catecholamines (adrenaline and noradrenaline)
1
Zone glomerulosa
2
Zone fasciculata
3
Zone reticularis
4
Medulla
True/false: all of the adrenaline in the blood comes from the adrenal medulla.
True
True/false: all noradrenaline in the blood comes from the adrenal medulla.
False
Noradrenaline comes from two sources: the adrenal medulla, and postganglionic sympathetic neurones.
Describe how the sympathetic nervous system can cause both constriction and dilation of arterioles.
- Sympathetic tone keeps the arterioles constricted to 50% of their diameter
- Increased stimulation → more constriction
- Decreased stimulation → less constriction
- The sympathetic nervous system is the body’s dominant mechanism for maintaining vascular tone.
Describe the synthesis pathway for adrenaline and noradrenaline
- Synthesis begins with the amino acid tyrosine, which is converted in a reaction catalysed by tyrosine hydroxyls (the rate limiting step)
- Further down the pathway, dopamine can be converted to noradrenaline, which can then be converted to adrenaline
True/false: the adrenal medulla secretes adrenaline and noradrenaline in equal amounts.
False
80% adrenaline
20% noradrenaline
What is the half life of catecholamines in plasma?
Very short: 1-3 mins
Describe the metabolism and excretion of catecholamines.
- Metabolised by the liver and kidneys
- Excreted via the urinary system. We can measure the amount of unmetabolised adrenaline and noradrenaline from this system.
A neurone is adrenergic if…
it secretes noradrenaline
e.g. postganglionic sympathetic neurones
A neurone is cholinergic if…
it secretes acetylcholine
e.g. most neurone with cell bodies in the CNS are (generally) cholinergic
Describe the types of adrenergic receptors
- Alpha adrenergic receptors
- Beta adrenergic receptors
- There are further subgroups: ɑ1, ɑ2, β1, β2
- Their effects can allow cells to be stimulated or inhibited
- Some cells have alpha and beta receptors, others have only one type (e.g. cardiac myocytes have only beta receptors)
What is the advantage of having different adrenergic receptors (alpha and beta) in different places?
Allows different effects on different tissues when stimulated e.g. constriction vs dilation
Describe the effect of catecholamine binding on alpha adrenergic receptors
- Vasoconstriction
- Pupil dilation
- Intestinal relaxation
- Pilomotor contraction
- Bladder sphincter contraction
Describe the effect of catecholamine binding on beta 1 adrenergic receptors
- Increased HR
- Increased contractility
Describe the effect of catecholamine binding on beta-2 adrenergic receptors
- Vasodilation
- Bronchodilation
- Glycogenolysis
- Lipolysis
True/false: catecholamines often bind to receptors and activate second messengers.
True
- The receptors are often G-protein coupled
- There are multiple second messenger pathways including adenylyl cyclase, phospholipase C, IP3, DAG, ion channels
Describe how SNS activation can lead to differing effects on different tissues
- Tissue response varies according to type and density of receptors, and relative concentrations of adrenaline and noradrenaline locally
- SNS activation
- In the intestines, alpha receptors are stimulated, causing smooth myocytes in blood vessels to constrict (vasoconstriction)
- In the muscles, beta 2 receptors are stimulating, inhibiting the same smooth myocytes and thus resulting in vasodilation
- The appropriate response thus occurs: reduced blood flow to the intestines, increased blood flow to the muscles.
Describe the importance of medullary hormones to fight or flight
- Medullary adrenaline and noradrenaline have the same general effects as the sympathetic nervous system. In fight or flight, there is widespread and simultaneous stimulation of tissue via both nervous and endocrine systems.
- Medullary hormones result in additional effects on tissues without direct sympathetic innervation e.g. metabolic actions appropriate for fight or flight.
Describe the metabolic actions of catecholamines
- Goal: increase amount of readily available energy substrate. This can be achieved through mobilisation of glucose or fatty acids.
- Catecholamines increase glycogenolysis in liver and skeletal muscle = increased glucose availability
- Catecholamines stimulate gluconeogenesis within the liver = increased glucose availability
- Catecholamines stimulate hormone-sensitive lipase (HSL) → stimulates hydrolysis of triglycerides in adipose tissues → higher circulating plasma fatty acids levels, used for energy through beta oxidation in mitochondria = lipid-derived energy
Describe how catecholamines supply essential tissues with energy substrates
- Increase available substrate through metabolic actions (provision of glucose/lipid-derived energy)
- Increase HR and contractility
- Increase cardiac output and blood pressure
- Shift in perfusion to central circulation (reduced peripheral circulation)
Explain the importance of medullary adrenaline in the following categories:
- Metabolic stimulus
- Cardiac effects
- Blood vessels within muscle
- Metabolic stimulus: adrenaline has 5-10x greater metabolic effect than noradrenaline
- Cardiac effects: adrenaline has a greater effect on beta receptors (beta stimulation)
- Blood vessels within muscle: adrenaline acts on beta-2 receptors, causing vasodilation required for fight or flight. Noradrenaline acts on alpha receptors, causing strong vasoconstriction (shock)
What is stress hyperglycaemia and why is it relevant clinically?
- Lab blood results will show hyperglycaemia when the animal is stressed (thanks to SNS activation & fight or flight response)
- This presents difficulty with diabetes mellitus cases; take care not to misdiagnose stress hyperglycaemia as diabetes mellitus
Noradrenaline vs adrenaline: which has a more profound effect on blood vessels
Noradrenaline
It increases total peripheral resistance and raises BP
Noradrenaline vs adrenaline: which has a more profound effect on the heart?
Adrenaline
It increases HR and contractility, thus increasing cardiac output
Which receptors do the following drugs act on and what is their action?
Detomidine, medetomidine, xylazine, romifidine
- These drugs are selective alpha-2 receptor agonist
- They act on alpha-2 receptors, resulting in vascular effects (initial vasoconstriction), increased urine production due to reduced renin and vasopressin secretion
Which receptors does the following drug act on?
Dobutamine
Beta 1 receptors
(Dobutamine is a selective agonist)
Which receptors do the following drugs act on?
Clenbutarol, salbutamol, albuterol
Beta 2 receptors
(These drugs are selective agonists)
Which receptors does the following drug act on?
Dopamine
Alpha 1, Alpha 2, Beta 1
(Dopamine is a non-selective agonist)
Which receptors does the following drug act on?
Atipamezole
Alpha 2 receptors
(Atipamezole is selection antagonist)
Which receptors do the following drugs act on?
Adrenaline/epinephrine
Alpha 1, Alpha 2, Beta 1, Beta 2, Beta 3
(Adrenaline is a non-selective agonist)
Which receptors do the following drugs act on?
Noradrenaline (norepinephrine)
Alpha 1, Alpha 2, Beta 1
(Noradrenaline is a non-selective agonist)
