Block B Lecture 2: Distribution and Signalling of Adrenoceptors Flashcards
Does the sympathetic nervous system increase or decrease the breakdown of glycogen and why does it do this?
Increase - does this to get more energy to help avoid a traumatic event
(Slide 4)
How do different adrenoceptors cause different responses when they are all activated by the same neurotransmitters?
Via location. Different adrenoceptors cause diverse reactions in different tissues. Receptor subtypes are also located in different locations
(Slide 6)
What are 7 examples of effects which α-adrenoceptors have in different tissue locations?
Answers Include:
Peripheral blood vessels - constriction
Airways - contraction
Eye - contraction (dilution of pupil)
Liver - glycogenolysis
Sweat glands - sweating
Piloerector muscles - contraction
Stomach and Intestines - decreased contraction
(Above all caused by α1 subtype)
Pancreas - decreased insulin secretion (both α1 and α2 subtypes)
Neurons - inhibition of synaptic activity (α2)
(Slide 11)
What are 4 different effects that β-adrenoceptors have in different tissue locations?
Heart - Increased heart rate, force, and rate of contraction
Kidney - increased renin secretion (by constricting peripheral blood vessels)
(Both the above are cause by the β1 subtype)
Liver - glycogenolysis (both β1 and β2)
Stomach / gut - muscle relaxation
Blood vessels - vasodilation
(Both the above are caused by the β2 subtype)
(Slide 12)
What is a good mnemonic to remember the vascular actions of adrenoceptors?
ABCD1,2:
Alpha-1 receptors
Beta 2 receptors
Constricts
Dilates
Remember this and that lines 1 and 3, and 2 and 4 pair with each other
(Slide 17)
What pathway do Gq coupled receptors activate?
- The receptor is bound to by a signalling molecule, making the receptor undergo a conformational change, resulting in Gq being activated.
- Gq activates phospholipase C by directly binding to it.
- Phospholipase C hydrolyses phosphatidylinositol 4,5-bisphosphate (PIP₂) and cleaves it into 2 secondary messengers: Inositol trisphosphate (IP₃) and Diacylglycerol (DAG).
4a. IP3 diffuses into the cytoplasm and binds to IP3 receptors on the surface of the ER, leading to release of stored calcium ions (Ca²⁺) into the cytoplasm, activating several calcium-dependent signalling pathways, such as smooth muscle contraction
4b. DAG activates protein kinase C
- Protein kinase C phosphorylates several target proteins, leading to a range of downstream effects, such as cell growth, secretion, or metabolic regulation
(Slide 19)
What pathway do Gi coupled receptors activate?
- The receptor is bound to by a signalling molecule, making the receptor undergo a conformational change, resulting in Gi being activated.
- Gi directly inhibits the enzyme adenylate cyclase, resulting in cAMP levels being decreased
- Lowered cAMP levels reduces protein kinase A activity
- Decreased protein kinase A activity leads to a decrease in protein phosphorylation, which leads to reduced cell activity
(Slide 19)
What pathway do Gs coupled receptors activate?
- The receptor is bound to by a signalling molecule, making the receptor undergo a conformational change, resulting in Gs being activated.
- Gs directly stimulates adenylate cyclase leading to cAMP levels increasing
- Increased cAMP levels results in protein kinase A being activated
- PKA phosphorylates several target proteins leading to various downstream effects such as smooth muscle relaxation, an increased heart rate or insulin release
(Slide 19)
What is the mnemonic to remember what each of the g protein pathways do?
Gq - remember q for calcium
Gi - I stands for inhibit -> inhibits adenylate cyclase
Gs - S stands for stimulate -> stimulates adenylate cyclase
(Slide 19)
What is the mnemonic for remember what g protein is coupled to α, β, muscarinic, dopamine and histamine receptors?
QISS AND QIQ until your SIQ
Q - α1-receptors
I - α2-receptors
S - β1-receptors
S - β2-receptors
Q - M1-receptors
I - M2-receptors
Q - M3-receptors
S - D1-receptors
I - D2-receptors
Q - H1-receptors
(Slide 20)
What is an example receptors coupled to the same intracellular pathway resulting in different functional responses?
β1 receptors in cardiac smooth muscle activate protein kinase A, which phosphorylates L-type Calcium channels leading to increase force of contraction
β2 receptors in vascular and airway smooth muscle also activate protein kinase A, but this phosphorylates MLCK, resulting in it being inhibited which results in a decreased force of contraction
(Slide 22)
What are the 5 factors affecting which adrenoceptor response (e.g. vasoconstriction vs vasodilation) is dominant?
Sensitivity to catecholamines: i.e. if they prioritise binding adrenaline or noradrenaline
Concentration of catecholamines - e.g β receptors are more sensitive to adrenaline whereas α receptors are more sensitive to noradrenaline
Ratio of receptors - different in different vascular beds
Specific intracellular signalling system
Neuronal Uptake
(Slide 24)
What 2 pathways do α2-receptors activate in order to reduce neurotransmitter release / action potential firing?
- Gi inhibits calcium release via inhibiting protein kinase A activity (as it phosphorylates calcium channels, activating them). The reduced calcium influx then inhibits neurotransmitter release as calcium is crucial for vesicle release in synaptic transmission.
- Gi also activates potassium channels, leading to hyperpolarisation of the cell, which makes it less likely to fire an action potential, therefore reducing neuronal activity.
(Slide 25)
What is the baroreceptor reflex?
A key mechanism that helps maintain blood pressure homeostasis, when blood pressure rises, baroreceptors (stretch-sensitive receptors) in the aortic arch and carotid sinuses detect the increase and send signals to the brainstem (specifically the medulla). This results in the activation of pathways that decrease heart rate, dilate blood vessels, and lower blood pressure.
(Slide 26)
Do α2-adrenoceptors enhance or inhibit the baroreceptor reflex?
They enhance it
(Slide 26)
