L8 Autonomic Pharmacology Flashcards
What are the principal transmitters in the autonomic nervous system (ANS)?
Acetylcholine and Noradrenaline
These transmitters act upon nAChRs, mAChRs, α- and β−adrenoceptors.
What are the two main ways that drugs can target ANS receptors?
Indirectly (synthesis, storage, breakdown) or directly (agonists, antagonists)
Understanding the systems controlled by these receptors helps predict drug action.
What is the role of G proteins in receptor signaling?
G proteins modulate effector proteins, which can be ion channels or enzymes
This modulation helps predict cellular effects.
What are the effects of Gαs protein activation?
Increases adenylyl cyclase, cAMP levels, and protein kinase A (PKA)
Gαs is considered stimulatory.
What does Gαi protein activation lead to?
Decreases adenylyl cyclase, cAMP levels, and protein kinase A (PKA)
Gαi is considered inhibitory.
What is cAMP?
A second messenger, moves freely in cytoplasm
What are kinases?
Enzyme that Adds phosphates to molecules/proteins
Explain how G protein- coupled receptor signalling works
1) Hormone or neurotransmitter binds to receptor which causes a conformational change
2) Activates G heterotrimeric G protein (Gαi/ Gαs)
3) This interacts with adenylyl cyclase
4) Adneylyl cyclase converts ATP to cAMP which activates PKA
What effect does Gαq have on intracellular calcium levels?
Increases intracellular Ca2+ levels through phospholipase C
This results in increased IP3 and DAG.
What are gαs, gαi and gαq all types of?
They are all different types of G protein alpha subunits
What effect does Gβy have in membrane potential?
They can directly influence membrane potential by interacting with and activating ion channels, specifically potassium channels
What are the two types of subunits within the Gi protein?
Gαi (inhibitory effects for cAMP)
Gβγ (activates potassium channels)
What are the main subtypes of muscarinic receptors?
M1, M2, M3, M4, M5
M1, M3, and M5 are coupled to Gq, while M2 and M4 are coupled to Gi.
Which subtypes of muscarinic receptors are coupled to Gq and Gi?
- M1, M3, M5 are coupled to Gq ( Increase calcium conc)
- M2 and M4 are coupled to Gi (inhibitory cAMP) and increases potassium channel opening
The effects of Muscarinic actions closely resembles what?
It closely resembles the effects of parasympathetic innervation
Where are Muscarinic receptors primarily located?
They are located postsynaptic to the parasympathetic ganglion neuron and in the sweat glands
What are Muscarinic receptors?
They are a type of GPCR that are activated by the neurotransmitter acetylcholine
Where are M2 (cardiac) located?
M2 receptors are located in nodal tissue and atria.
Where are M3 (glandular/smooth muscle) generally located?
- Exocrine glands: salivary, etc
- Smooth muscle: gastrointestinal tract, eye, airways, bladder
- Blood vessels: endothelium
What is M3’s (glandular/ smooth muscle) main functional response?
- Gastric, salivary secretion
- Gastrointestinal smooth muscle contraction
What is the primary function of M2 muscarinic receptors?
Decreases heart rate and slows atrioventricular conduction (decrease force of atria contraction)
Cardiac inhibition
How does M2 decrease heart rate?
- M2 activation via ACh
- Gαi protein activation
- βγ subunits open potassium channels
- Potassium ions move out of the nodal cell into the ECF
- More negative membrane potential which makes it more difficult for cell to reach threshold potential
What physiological response is stimulated by M1 and M3 muscarinic receptors?
Contraction of smooth muscle and secretion from exocrine glands
This includes bronchoconstriction and gastrointestinal motility.
What is a common effect of muscarinic agonist overdose?
Death from cardiac and respiratory failure
Symptoms may include decreased blood pressure, increased saliva, tearflow and sweating
