Adenoreceptors and Beta-Adenoreceptor Antagonists Flashcards
What releases adrenaline?
sympathetic nerves
What releases adrenaline and noradrenaline?
adrenal medullae
What are the tow main sub-types that catecholamines bind to?
- α adrenoreceptors
- beta adrenoreceptors
From the two main subtypes, how are the adrenorecpetors further divided into 5 groups? (two α groups and 3 beta groups)
- depending on the agonist potency order
- e.g is it more sensitive to noradrenaline or adrenaline
Why are adrenoceptors describes as G protein coupled receptors?
they recruit intracellular G proteins in order to produce their cellular effects
What is the difference between α and beta adrenoceptors?
recruit different intracellular proteins so have different intracellular effects
What are some features of a G protein coupled receptor?
- intracellular loop
- crosses membrane seven times
- C terminal and N terminal are on opposite sides of the membrane (n terminal outside)
- area of receptor able to bind a signalling molecule (ligand binding domain)
- G protein coupling domain
What are the three subunits that G proteins consist of?
- α
- beta
- gamma
What happens when an agonist e.g noradrenaline binds to a G protein coupled receptor?
The GDP on the G protein coupled receptor changes to GTP high destabilises the G protein. The α subunit disassociates from the beta and gamma subunits. α subunit diffuses through the membrane to interact with a target protein which will generate an effect
(NB it is possible for the beta, gamma subunit to be the active form but its usually the α form)
What happens in α1 adrenoreceptor the Gq protein coupled receptor pathway?
-Noradrenaline binds to the α1 receptor
-target for Gq α subunit is phospholipase C
-phospholipase C it takes phosphotyl inositol and coverts it into IP3 and DAG which will cause a different effect
-IP3 binds to a receptor on the ER which increases calcium release
-this increases the Ca2+ conc inside the cell and if it is a muscle cell it will cause contraction
(this is linked to the α1 receptor)
What is the α2 receptor pathway?
- α2 receptor is coupled to the Gi protein (inhibitory)
- Gi is coupled to adenyl cyclase which it inhibits
- this results in decreased cAMP levels
- decreased activity of protein kinase A
- decreased phosphorylation of intracellular proteins
- effect depends on cell
What is the beta adrenoreceptors pathway?
- Beta receptor associated to Gs protein (stimulation)
- the Gs α subunit when activated, stimulates adenyl cyclase
- increased cAMP levels
- increased activity of protein kinase A
- increased phosphorylation of intracellular proteins
- effect depends of cell type (smooth muscle causes relaxation)
What is the relationship between α2 receptors and beta receptors interesting?
-the same neurotransmitter (noradrenaline) can cause different effects depending on what receptors are present
How can we target particular organs using drugs?
-each organ will have different types of receptors so if you know the receptors, you can target drugs
What is the important type of adrenoreceptors in the cardiac system?
beta 1
