Receptors Flashcards
What are the 4 classes of proteins targeted by drugs?
Enzymes
Transporters
Ion channels
Receptors
Define Receptors
Proteins that serve as recognition sites and allow binding of chemical mediators
What is the function of receptors ?
Regulation of cellular processes
Chemical recognition and binding
Intracellular signal generation
Name 2 drugs which interfere with ion channels
Lignocaine (voltage gated sodium channel blocker)
Gabapentin (voltage gated calcium channel blocker)
How many aa segments do transmembrane receptors span?
20-25 hydrophobic amino acids
What is a type 1 receptor?
Ligand gated ion channel
Is a type 1 receptor ionotropic or metabotropic?
Ionotropic
How do drugs interact with membrane receptors ?
Via the extracellular ligand binding domain, travels through the transmembrane segments, into the cytoplasm via the cytoplasmic domain
What is the type 2 receptor?
G-protein coupled receptor
Is the type 2 receptor ionotropic or metabotropic?
Metabotropic
What is the effector for a type 1 ?
An ion channel
What is the effector for type 2?
Channel or enzyme
What is the type 3 receptor?
Receptor kinase
What is the type 4 receptor?
Nuclear receptor
How does a type 4 receptor couple?
Via DNA
How is a type 4 different to type 1,2&3?
Type 4 is an intracellular receptor whereas the others are all membrane receptors
Define ligand
Any molecule that binds to a receptor
Define an agonist
An agonist produces a response in the cell after binding to a receptor
Define an antagonist
An antagonist inhibits or prevents a response after a possible receptor binding
How does a type 4 receptor work?
Soluble receptors that sense lipid and hormone signals and modulate gene transcription. The binding ligand must be able to cross the plasma membrane
Give an example of an agonist
Pilocarpine
Nicotine
Acetylcholine
Morphine
Give an example of an antagonist
Atropine
Curare
How does type 1 transduce a signal ?
Hyperpolarisation or depolarisation
How does type 2 transduce a signal?
Change in excitability or
Second messengers (protein phosphorylation, Ca2+ release/other) which produces a cellular effect
How do type 3 transduce a signal?
Protein phosphorylation ->
Gene transcription ->
Protein synthesis ->
Cellular effects
How does type 4 transduce a signal?
Ligand binds to receptor in the nucleus ->
Gene transcription ->
Leaves nucleus and protein synthesis occurs ->
Cellular effects
Example of type 1
Nicotinic ACh receptor
Example of type 2
Muscarinic ACh receptor
Example of type 3
Cytokine receptor
Example of type 4
Oestrogen receptor
What is an ionotropic receptor?
Receptors that are ion channels
What is an endogenous agonist?
Fast/classical neurotransmitters stored in synaptic vesicles, composed of 3-5 subunits with a central aqueous pore.
When does a channel close?
When an agonist is removed or
When a receptor enters a desensitised state
What does activation of ionotropic receptors by excitatory neurotransmitters cause? Give an example and its antagonist
Membrane depolarization
Action potential firing
Example: Nicotinic Acetylcholine Receptor, antagonist = tubocurarine
What does activation of ionotropic receptors by inhibitory neurotransmitters cause? Give an example
Inhibits membrane depolarisation
Reduces action potential firing
Example: GABAaRs
Structure of type 1
Pentameric assembly
Cys-loop type
Structure of type 2
Tetrameric assembly
ionotropic glutamate type
Structure of type 3
Trimeric assembly
P2X type
Structure of type 4
Tetrameric assembly
Calcium release type
Why may cells express different receptors?
To coordinate their responses to changes in external environments and maintain homeostasis
What does the physiological consequence of a drug rely on?
Specificity
