Wheatley - Ligand Binding Flashcards
Describe two broad functions of Acetylcholine
Acetylcholine acts as a neurotransmitter at the neuromuscular junction for the conduction of muscles and in the autonomic nervous system.
It is also used internally as a final product in the parasympathetic nervous system.
What are the two broad groups of acetylcholine receptors?
Muscarinic (mAChR) and Nicotinic (nAChR)
What are the agonists and antagonists of the acetylcholine receptors?
For Muscarinic: muscarine (agonist) and atropine (antagonist)
For Nicotinic: nicotine (agonist) and curare (antagonist)
Give a brief description of nicotine
Nicotine is an alkaloid of the nightshade family and a stimulant drug. It is an nAChR agonist and has particularly high affinity for a2b4 receptor and acts as an antagonist for nAChRa9 and nAChRa10.
Give a brief description of muscarine
Muscarine is derived from mushrooms and acts as a potent non-selective mAChR agonist. Its potency is underpinned by its resistance to breakdown by Achetylcholinesterase.
Define “agonist” and “antagonist”
An agonist is defined as a compound which upon binding to a receptor generates a response.
An antagonist is defined as a compound which upon binding to a receptor generates no response.
What are the Nicotinic receptor isoreceptors and what subunits are they composed of?
NAChRs can be divided into muscle and neuronal subtypes:
The muscular subtypes are composed of alpha, beta, gamma, delta in a 2:1:1:1 ratio (embryonic) and alpha, beta, gamma, epsilon is a 2:1:1:1 ratio (adult).
The neuronal subtypes are various homo/heteromeric combinations of 12 subunits, alpha2-alpha10 and beta2-beta4.
What are the Muscarinic isoreceptors and how are they all different? Where are they located?
There are five isoreceptors: M1, M2, M3, M4, M5
M1, M3, and M5 are coupled to Gq proteins
M2, M4 are coupled to Gi/o proteins
They are encoded by CHRM1, 2, 3, 4, 5 genes respectively.
M1 located in ganglionic nerve, CNS, stomach. M2 located in the heart and CNS. M3 located in many locations (eye, CNS, smooth muscle etc). M4 and M5 located in the CNS.
What are the subtypes for the Adrenergic receptors?
Alpha Adrenergic receptors : alpha1a, alpha1b, alpha1d, alpha2a, alpha2b, alpha2c
Beta Adrenergic receptors: beta1, beta2, beta3
How many 5-HT isoreceptors are there and how are they categorised?
There are 14 in total, and they are divided into 7 categories. All are GPCRs except 5-HT3 which is a ligand gated ion channel. All have excitatory potential except 5-HT1 and 5-HT5 which possess inhibitory potential. Encoded by respective HTR genes.
5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F 5-HT2A, 5-HT2B, 5-HT2C 5-HT3 5-HT4 5-HT5A, 5-HT5B 5-HT6 5-HT7
What are the axis of a dose-response curve and what is the shape like?
[ligand] vs. response. Hyperbolic.
What do the shapes look like on a [ligand] vs. response curve for partial, full and superagonists?
All show hyperbolic relationships. From partial to full to super, the maximal response is raised.
If you plot log[ligand] vs. Response, what shape will you achieve?
Sigmoidal
Upon additional of irreversible antagonist to a system, how will the log[ligand] vs. Response change?
An irreversible antagonist will reduce gradually the number of free receptor availability. This will initially be visualised a subtle left -> right shift of the sigmoidal graph due to spare receptor phenomenon, and with addition of more ligand there will be then a dampening down of the line and a reduction of maximal response once all spare receptors have been used up.
