Receptors Flashcards
What is a receptor
A protein that recognises and creates a response to Environmental stimuli
Receptor classes
Ligand gated ion channel(Inotropic)
G protein coupled receptors(metabotropic)
Kinase linked
Nuclear receptors
Agonist
A chemical that binds to a receptor to activate it causing a biological response
Active AR complex
Agonist+receptor= Active AR complex
causes a conformational change in the receptor causing agonist induced response
Drug Agonist types
Full agonist-Receptor fully activated
Partial agonist-Activates receptor partially
Affinity
The strength in attraction between the receptor and the agonist.
Smaller kd means higher affinity
Efficacy
The maximum biological affect(Emax)
Partial agonist have low efficacy
Potency
Potency is the concentration required to reach 50% of maximal effect(EC50)
Depends on the affinity
Anxiolytic affect
When partial agonist binds it causes anxiolytic affect therefore having anti anxiety affect whereas a full agonist has sedation effect
Inverse agonist
Binds to the same receptor as an agonist but induces an effect opposite to an agonist. It occurs to the receptors with constitutive activity(basal activity)
Spare receptors
receptors that exist in excess of those required to produce a full effect
Antagonist
A receptor that binds to a receptor but does not activate it
Antagonist classes
Reversible-Competitive/non-competitive
Irreversible
How to overcome competitive antagonist
Increasing agonist concentration or decreasing antagonist
Competitive antagonist effect
Parallel shift to the right but no change to slope
Schild Plot
Schild Plot is used to compare the different affects of the antagonist to the receptor.
PA2
Shows how competitive an antagonist is
If there is a competitive agonist the slope should be 1
You can also tell how potent and effective the antagonist is
The smaller the PA2 the better it binds to the receptor
Non-competitive antagonist
binds to the allosteric site
Haxamethonium blocks the ion channel of the nicotinic receptor
Irreversible competitive antagonist
This antagonist dissociate very slow from the receptor
Increasing concentration does not increase response
Binds to the receptors using covalent bonds
Irreversible competitive antagonist as non-surmountable
The inhibition is non-surmountable(The proportion of receptors occupied by the antagonist is lost by the agonist
Maximum response is decreased
Specificity
Measures how well a drug can discriminate between different receptors. Low specificity can cause side effects as it causes responses to multiple receptors
scatchard plot
We use a scatchard plot to find the Kd specificity
KI
KI value is used to characterise the ability to inhibit agonist binding to the receptor
GPCRS
G-protein-coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors in eukaryotes
Structure of GPCRS
There are Kinks in TM5-7 allowing for the conformational change
The largest conformational change in TM6 moving outwards from the central TM3 BY 14A
The small P(288 and 211) are proline residue they are hydrophobic residue and cause them to bend at these sites
Ligands
Ligands bind to GDPR
Ligands include light-sensitive compounds, odors, pheromones, hormones and neurotransmitters
Lgands usually bind to extracellular sides
Ligands
Ligands bind to GDPR
Ligands include light-sensitive compounds, odors, pheromones, hormones and neurotransmitters
Lgands usually bind to extracellular sides
Forces in ligands
Ionic
Hydrogen
Hydrophobic
Steric factors
Receptor signal transduction
Agonist bind to receptor
Receptor conformational change via TM5,6,7
GPCR signalling
G proteins relay signal from GPCR to secondary messengers
G protein subunits
Alpha-Main role in activating effectors
Beta
Gamma
Ga protein signalling
Ga activates cAMP
cAMP then activates PKA
PKA phosphorylates other substances
GPCR desensitisation
When a receptor is constantly bound to by a agonist causing response to be lower overtime
Homologous desensitisation
desensitisation caused by phosphorylation of GPCR via PKA
