1 - Receptor Families and Ligands Flashcards
What is pharmacokinetics and pharmacodynamics?
Pharmacokinetics - What the body does to the drug
Pharmacodynamics - What the drug does to the body?
What are the four types of ways cells signal to one another?
What is autocrine signalling?
A cell secretes a ligand, which then acts on a receptor on the same cell that secreted the ligand
What is a receptor and a ligand?
Receptor: A molecule that recognises a ligand and in response to ligand binding, brings about a regulation of a cellular process
Ligand: A molecule that binds to a specific receptor
What is an agonist and antagonist?
Agonist: A ligand that when bound to a receptor, activates the receptor, so it begins regulating a cellular process.
Antagonist: A ligand that binds to a receptor but cannot acitvate it
What are the roles of receptors?
- Signalling
- Modulating immune response
- Releasing intracellular calcium stores
- Neurotransmission
- Cellular delivery
- Cell adhesion
- Control gene expression
What is the affinity (Km) of a receptor?
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The concentration of ligand needed to fill half the receptor sites.
(Higher than Km of substrate/enzymes)
TIGHT BUT REVERSIBLE
How are receptors classified?
1st - Agonist that binds to them
2nd - The antagonist that has the highest affinity
What type of molecules bind to nuclear receptors?
Small hydrophobic, e,g sex and steroid
What is an acceptor?
Still operates in absence of a ligand
What are the four receptor nuclear families in order of fastest to slowest?
- LGIC
- Catalytic
- GPCR
- Nuclear
What is the structure of a classical LGIC and how does it work?
Ligand binds allosterically to receptor, causing a conformational change. This opens the gated pore so ions can diffuse in
What is the structure of a GPCR and how does it work?
- Ligand binds causing change in shape of receptor, activating it so has higher affinity for G protein
- G protein binds, causes change so changes affinity for GDP so GDP disassociates and GTP associates
- A-GTP subunit dissociates and goes on to activate transducers by phosphorylation
What is the structure of a catalytic (TK) receptor and how does it work?
- Agonist binds to ligand binding domain
- Dimerisation of receptors
- Autophosphorylation
- YP can then phosphorylate enzymes and transducers, activating them
Why is the insulin receptor different to the normal catalytic receptors?
Made up of 4 proteins not 2
If an agonist is bound to a receptor, why can there be no change in the regulation of a cellular process?
- Receptor is an inhibitory cellular process
- Integrated signalling
What is the structure of an intracellular receptor and how does it work?
- Ligand binds to LBD, changes shape of it so releases inhibitory protein
- DBD free to bind to DNA and regulate transcription
Name a few ligands for each receptor family.
- GPCR - Adrenaline, Acetylcholine
- LGIC - Nicotine, IP3
- Catalytic - Insulin, GF’s
- Nuclear - Oestrogen, Cortisol, Vit D, Thyroid Hormone
Name a type of receptors for each receptor family
- LGIC - Nicotinic Acetylcholine
- GPCR - Muscarinic Acetlycholine
- Catalytic - Tyrosine Kinase
- Nuclear - Oestrogen
What are some examples of agonists and antagonists?
Agonist:
- Asthma: Salmeterol/Salbutamol. B2 adrenoreceptor and cause bronchodilation
- Analgesia: Morphine, U opiod
Antagonist
- Anti-hypertensives (Atenolol): B1 adrenoreceptors, block intropy of heart, decreasing b.p
- Haloperidol: D2 Dopamine, neuroleptic
Why is signal amplification important?
Converts nanomolar signals to millimolar responses
- Speed
- Multiple pathways triggered
