Unit 4 - Receptor pharmacology Flashcards
What is an antagonist?
Bind to the receptor in such a way that they produce a different induced fit and do NOT activate receptor
- block natural messenger so cannot bind and activate
What is an agonist?
Bind to the receptor binding site in a similar way to the natural messenger and activates receptor
What is selectivity?
Relative affinity
- ligand has higher affinity for one receptor over another
Ligand will preferentially bind to one receptor more avidly than another
- at a lower concentration
What effect does better selectivity have?
Fewer side effects
Give examples of selective and non selective drugs
Atenolol - selective B1-adrenoceptor antagonist
Propranolol - non-selective B1-adrenoceptor antagonist
What effect does a drug with a low affinity have?
Need to have a higher concentration of drug to produce a response
How can selectivity be observed?
Response profiles - not used any more Concentration response curves Radioligand binding - direct method of measuring affinity of ant/agonist for a receptor
How are most receptors distributed?
Most receptors are not ubiquitously distributed
- distributed in discrete tissues/organs in the body
How is assaying selectivity carried out?
Different tissues can express different populations of receptor types
How do non-selective drugs affect tissues?
Non-selective drugs affect all tissues
How do selective drugs affect tissues?
Selective drugs affect some tissues but not all tissues
- response in SOME tissues
What type of adrenoceptor subtypes are found in the heart?
Beta 1
Beta 2
What effect does adrenaline have on beta 1 and beta 2 adrenoceptors in the heart?
Adrenaline is non-selective
- will affect both types of receptor
- heart rate increases
- coronary flow increases
- vasodilation
What effect does dobutamine have on beta 1 and beta 2 adrenoceptors in the heart?
Dobutamine is selective for Beta 1 adrenoceptor
- heart rate increases
- no effect on coronary flow
What effect does salbutamol have on beta 1 and beta 2 adrenoceptors in the heart?
Salbutamol is selective for Beta 2 adrenoceptor
- no effect on heart rate
- coronary flow increases
- vasodilation
How can selectivity be revealed in tissue containing different receptor subtypes?
Concentration response curves
- non-selective agonist
- affinity for receptor is pretty much the same
- sees entire receptor population as the same so targets equally
- selective agonist
- multiple curves
- 2 stacked on top of each other
- 2 EC50 values
- 2 affinity types
What is the function of radioligand binding?
Determines binding affinity of ligand for binding site
Affinity is a constant for a ligand-binding site
- receptor
- EXCEPTION
- different affinity states due to G-protein binding
Efficacy is NOT a factor
- no distinction between agonists and antagonists
What are the two types of radioligand binding?
Saturation
Competition binding
What is saturation binding?
Add radioligand to sample of tissue
- drug labelled with radioactivity
Wash unbound drug away
Measure the amount of radioactivity from sample
What is specific binding?
Only interested in binding to the receptor
- specific
Describe specific binding
Saturable
- finite number of receptors to bind to
- upper limit
- the number of receptors present
- plataeu when all the receptors are full
Describe non-specific binding
Non-saturable
- will always increase with increasing addition of ligand
What can be worked out from saturation binding?
Dissociation constant, KD - affinity constant, KA - 1/KD Maximum specific binding - total number of receptors present
What is competition binding?(radioligand)
Add one concentration of radioligand
Displace radioligand from receptors with unlabelled ligand
- increasing concentration of unlabelled ligand
Radioligand and ‘cold’ ligand can be the same
- simplifies things
- but often use known radioligand with known affinity for receptor
Affinity is calculated based on the relative affinities and concentration of radioligand
- known concentration and affinity of radioligand
