ELM 2.1 Flashcards
How many subtypes of muscarinic receptors are there?
5
Choline acetyltransferase is located:
In the cytoplasm
Presynaptic nerve terminals have specific transporters for__________ in their membranes.
choline
Where are nicotinic acetylcholine receptors found? (3)
- skeletal neuromuscular junction
- central nervous system
- autonomic nervous system
In nicotinic receptors, what subunit exists rather than the epsilon subunit in fetuses?
gamma
What makes up the pentamer in skeletal muscle nicotinic receptors?
2 alpha 1 subunits, an epsilon subunit, and delta, and a beta 1 subunit
Neuronal nicotinic receptor (alpha 4, beta 7, alpha 7 subtypes) are located where? and what is their role
Pre-synaptic nerve terminals and on neuronal axons
Role: neuronal modulation - modulate the release of ACh and other neurotransmitters
Autonomic nicotinic receptors (alpha 3 and beta 4) - their roles are what?
Similar to that in skeletal muscle - trigger an action potential in post-ganglionic neuron and ensure the signal is sent down to autonomic effector tissues
Which transmembrane domain in the nicotinic acetylcholine receptor subunits forms the lining of the ion channel?
2
How many binding sites for acetylcholine are there in the muscle nicotinic receptor?
2
How is signalling via acetylcholine terminated at the neuromuscular junction?
enzymatic degradation of the signal (ACh is broken down by acetylcholinesterase - this is the same process at all cholinergic terminals)
Where is the agonist binding site in nicotinic receptors?
In the terminal domains (the N terminus)
Where is the agonist binding site in family A receptors?
Buried down in the transmembrane domains
Agonists in M1 receptors could potentially be used to treat what? (2)
Alzheimer’s Disease + Schizophrenia
Antagonists at the M1 receptor could potentially be used to treat what?
Potential therapies for certain cancers
What is darifenacin useful for?
30 fold M3 selective (overactive bladder)
Where are colinergic neurons present?
Cholinergic neurons are present in the CNS and also play major roles in the autonomic nervous system (particularly the parasympathetic branch)
Muscarinic M2 and M4 receptors can act as what?
As presynaptic autoreceptors.
What do muscarinic M2 and M4 receptors do, and what kind of feedback loop is this?
They inhibit the release of ACh from the presynaptic nerve terminal. This is a form of negative feedback
The post synaptic cell can be what?
Any tissue innervated by the parasympathetic nervous system e.g. smooth muscle, cardiac muscle, gland. Muscarinic receptors are also found in the CNS, so this could also be another CNS neuron.
Describe the function/applications of muscarinic agonists
They are not widely used, but many potential applications for antagonists as mAChR are widespread in the parasympathetic NS and the CNS.
Describe the function/applications of muscarinic antagonists
Peripheral effects mostly by blocking the parasympathetic nervous system = parasympatholytic drugs
Describe atropine (3)
- non-selective
- treats bradycardia (M2 receptors SA node)
- nerve agent antidote
Describe hyoscine (scopolamine) (3)
- non-selective
- nausea, motion sickness, IBS
- mods reduce blood brain barrier penetration
Describe ipratropium/tiotropium
- target
Describe ipratropium/tiotropium (2)
- target M3 receptors in bronchial smooth muscle
- used in COPD and asthma
Describe glycopyrrolate (glycopyrronium) (4)
- non-selective
- used as surgery premedication
- given with AChE inhibitors
- can treat excessive sweating
Describe benzatropine (benztropine) (2)
- M1 selective antagonist
- treats movement disorders (parkinson’s)
Describe darifenacin (2)
- M3 selective (30-fold vs M2)
- used to treat overactive bladder syndrome
Describe cyclopentolate/tropicamide (3)
- used to produce mydriasis (pupil dilation) and cycloplegia (paralysis of accommodation)
- shorter duration than atropine
- causes light sensitivity
Which muscarinic receptor subtypes couple to the IP3 pathway via Gq?
M1, M3, M5
Which muscarinic receptor type is heavily expressed in the heart?
M2
Where is the allosteric site on muscarinic receptors?
Just above the agonist binding site
What are the alpha agonist potency rankings?
noradrenaline > adrenaline > isoprenaline
What are the beta agonist potency rankings?
isoprenaline > adrenaline > noradrenaline
What enzyme is involved in the breakdown of noradrenaline?
Monoamine oxidase - located on the mitochondrial membrane - regulates the pool of releasable noradrenaline
What protein is key to terminating signaling at adrenergic synapses?
NET (norepinephrine transporter)
Precursors of noradrenaline include: (3)
- dopamine
- tyrosine
- L-DOPA
Adenylate cyclase and phospholipase C are the enzymes that initiate signalling via cAMP and IP3 respectively. Which subtypes of adrenoceptor have stimulatory effects on these enzymes? (3)
Alpha 1, Beta 1, Beta 2 : alpha 1 is coupled to Gq and stimulates PLC and the beta receptors both stimulate adenylate cyclase via Gs
From what region do the parasympathetic neurones that target the lower GI tract leave the spinal cord?
sacral
When a parasympathetic neuron makes a synapse with its target tissue, which neurotransmitter does it usually release?
Acetylcholine
