Flashcards in Physiological systems to Molecular drug targets Part 2 Deck (22):
Where do the vast majority of postganglionic sympathetic fibres release noradrenaline to act on?
1. Alpha adrenoceptors
2. Beta adrenoceptors
Where is noradrenaline release regulated?
Inhibitory presynaptic alpha 2 adrenoceptors
Where is noradrenaline released and how can you identify it compared to other catacholamine/biogenic amine structure?
1. Released by post ganglionic sympathetic nerves
2. Benzenediol and methyl amine group attached
What is produced during the negative feedback on noradrenaline? Why is this good?
1. Tyrosine hydroxylase
2. Can easily restart the change and go back unlike adrenaline
What are some examples of catacholamine/biogenic amine groups?
Why is tyrosine hydroxylase such an important enzyme?
It's the starting point to producing DOPA, dopamine, Noradrenaline and adrenaline
What is the location and function of the B1, B2 (most important) and B3 receptors?
1. B1 - heart - increases cardiac rate and force
2. B2- Smooth muscle heart, skeletal muscle and nerve terminals - vasodilation and bronchodilation
3. B3- Skeletal fat muscle- Thermogenesis and Lipolysis
What G protein and response do beta 1, 2 and 3 represent?
1. They all are G alpha S
2. They all Increase in cyclic AMP
Explain how the GPCRS in G alpha S (beta 1,2,3) stimulate adenylate cyclase?
1. The addition of G alpha S and GTP leads to the stimulation of adenylate cyclase
2. Leads to ATP converting to cAMP
What effects can cAMP have and what can this lead to in the beta 1 and 2 receptors?
1. cAMP can increase protein phosphorylation
2. Beta 1:
Increased cardiac muscle contraction
cAMP activates protein kinase A
3. Beta 2:
Decreased smooth muscle contraction
cAMP inhibits myosin light chain kinase
What is the three agonist potents in beta 1, 2 and 3?
What is the main selective agonists for B2 receptors?
What is the main selective agonists for B1 receptors? and antagonists?
Explain the main cardiovascular effects the noradrenaline can have?
1. Alpha selective which causes vasoconstriction (alpha 1)
2. Leads to reflex of bradycardia (baroreceptor response) due to ACh action at the vagal nerve
3. Overall increase in blood pressure
Explain the main cardiovascular effects the isoprenaline can have?
1. Beta selective which predominantly causes vasodilation (beta 2) and tachycardia (beta 1)
2. Overall decrease in blood pressure
Explain the main cardiovascular effects adrenaline can have?
1. Immediate action and low concentration
2. Leads to an increase in blood pressure
Explain how the adrenergic transmission occurs in the synapse?
1. Thousands of varacosities (means swelling)
2. Tyrosine hydroxylase is converted to noradrenaline
3. Alpha 2 receptor causes a negative response and is uptaken in the "1" transport system
How do we block the "1" and "2" transport systems?
- psuedoephedrine amphetamine
- Tricyclic antidepressants (blocks build up of noradrenaline)
How does psuedoepherdrine work?
1. Selectively effects the uptake "1" transport system as it mimics the structure of noradrenaline
2. Takes up psuedoepherdrine instead of noradrenaline which causes a build up in the synaptic cleft
3. Noradrenaline causes vasoconstriction which reduces oedema in the nose so acts as a nasal decongestant
Where is the location of the alpha 1 adrenoceptor and the function of it?
1. Location: smooth muscle
- Contraction (relaxes GI tract)
Where is the location of the alpha 2 adrenoceptor and the function of it?
- smooth muscle
- nerve terminals
- inhibition of transmitter release