Receptor Mechanisms Flashcards
What are the four super-families of receptors?
- Ligand-gated ion channels
- G-protein coupled receptors
- Kinase-linked receptors
- Nuclear receptors - intracellular
In order of speed of response with fastest at top and slowest at bottom
Which family is the fastest?
Ligand-gated ion channels
- Forms an aqueous pathway upon binding of the drug/ligand
- Conformational change - allowing the immediate flow of ions
- Causes change in membrane potential due to depolarisation/hyperpolarisation
Name 4 ligand-gated ion channels and their agonists. List the ions involved and the subsequent effect on membrane potential.
- Nicotinic Cholinoceptor (stimulates by Acetylcholine)
- 5HT3 (stimulated by 5-HT, serotonin)
- GABA(A) (stimulated by γ-amino butyric acid (GABA))
- Glycine receptor (stimulated by Glycine)
For the Nicotinic and 5HT3, the ions are Na+/Ca 2+. Causes depolarisation - excitatory response in neurones
For GABA(A) and Glycine, the ion is Cl-. Causes hyperpolarisation - inhibitory response in neurones
Outline the structure of a nicotinic receptor
- Large amino terminal end and short carboxyl-terminal end
- Most LGICRs are made up of 5 proteins (pentamer) - each consisting of 4 transmembrane domains
- Transmembrane domain 2 forms the lining of the aqueous ion pore through which the ions will pass through upon activation
- Binding site also present in which ligand binds to activate receptor
Where are the hydrophobic and hydrophilic amino acid regions situated in an LGICR?
- HYDROPHOBIC - kept within the bilayer to form transmembrane domains
- HYDROPHILIC - found in intracellular and extracellular regions i.e outside of membrane
How would a nicotinic ACh receptor(nAChR) be activated and what would happen upon activation?
- Agonists are 2 ACh molecules
- ACh binds to the alpha subunit
- Causes pore to enlarge i.e channel opens, rapidly forming an aqueous pathway -
- Ions move down an electrochemical gradient - influx of Na+ ions - excitatory junction potential formed - stimulates an action potential
- ACh may then be recycled or broken down by AChesterases
What are the two subtypes of nicotinic receptors?
- N1 or Nm - found in neuromuscular junction of skeletal muscle
- N2 or Nn - found in CNS(brain) or autonomic ganglia
What are the composition of N1 and N2 nicotinic receptors?
- Muscle nicotinic N1 AChRs (adult neuromuscular junction)
α1 - ε - α1 - β1 - δ - Muscle nicotinic AChRs (foetal extrajunctional) - stays open for longer - potentially due to γ protein
α1 - γ - α1 - β1 - δ - Neuronal (N2) nAChRs
α2-α8 and β2-β4
What is myasthesia gravis?
- Autoimmune disease in which the α1 subunit is degraded by antibodies
Considering that muscular nAChRs are broken down, why might myasthesia gravis cause muscle weakness?
- Reduced number of muscle nAChRs that are complementary to ACh due to degradation of alpha subunit
- Reduced binding of ACh therefore reduced activation and reduced formation of aqueous pathways and therefore reduced sodium ion influx
- Reduced electrical activity - therefore reduced formation of the excitatory junction potential
- Reduced stimulation of action potential which is needed for muscle contraction
Why does myasthesia gravis not affect neurones?
- Neuronal nAChRs are unaffected since no α1 subunit present
What are the steps when GABA(A) or glycine receptors are stimulated?
- Made up of 5 proteins
- Inhibitory nerves release GABA or glycine
- These bind, causing GABA(A) and glycine receptors to be stimulated
- Rapid formation of aqueous pathway and rapid influx of chloride ions
- Causes hyperpolarisation of membrane
- Cause inhibitory effects quickly
