Lecture 2.1: Structure & Classification of Receptors Flashcards
Why is cell signalling important?
It permits effective communication and regulation of cells and cellular processes
What are the steps in cell signalling?
Reception
Transduction
Response
Amplification
Receptors are proteinaceous, what does this mean?
Capable of selectively binding a ligand (therefore, responses are selective as well)
Receptor numbers are not static, what does this mean?
- Increased numbers of receptors =
upregulation (increased sensitivity) - Decreased numbers = downregulation
(desensitisation or tachyphylaxis) - Desensitisation occurs after a series of doses,
tachyphylaxis may occur after the first dose
What is a Ligand?
A molecule that binds to a receptor
Examples of Ligands
- Hormones
- Neurotransmitters
- Growth Factors
- Drugs
What is a ligand which binds and activates called?
Agonist
What is Agonist Potency?
[Agonist] needed to produce 50% maximal response
What is Agonist Efficacy?
Ability of an agonist, after binding, to activate receptors
What is a ligand which binds and blocks agonist binding called?
Antagonist
What is a which fails to produce maximal response on binding called?
Partial Agonist
What type of receptor is a Ligand gated ion channels?
Ionotropic Receptors
What type of receptor is a G protein-coupled receptors (GPCR)?
Metabotropic receptors
What type of receptor is an Enzyme-linked receptors?
Kinase-linked receptors
What type of receptor is an Intracellular receptors?
DNA-linked nuclear receptors
What type of receptor is a nicotinic receptor?
Ionotropic receptor
What us the structure of a nicotinic receptor?
- Formed from 5 subunits (2 a’s, 1
beta, 1 gamma, 1 delta) - There are 2 binding sites (on a’s)
that need to be occupied before
the receptor is activated
What is the role of ionotropic glutamate receptors?
Mediates the effects of the excitatory amino neurotransmitter Glutamate
What are the 3 Types of ionotropic glutamate receptors?
- NMDA
- AMPA
- Kainate
How many subunits is the NMDA receptor made from?
7 subunits (monomers)
How does the NMDA receptor work?
Highly permeable to Ca2+, and easily blocked by Mg2+ , receptor also requires glycine to bind
What is the role of the NMDA receptor?
- Significant roles in synaptic plasticity (learning,
memory also though pathophysiology e.g.
chronic pain) - Significant role in excitotoxicity caused by Ca2+
overload
Why are G-protein coupled receptors (GPCRs) called metabotropic receptors?
- Because they trigger chain of intracellular
reactions known as the second messenger system - The link to these second messengers are G-
proteins hence the name!
Examples of GPCRs (2)
- Adrenoreceptors (noradrenaline)
- Muscarinic receptors (acetylcholine)
Why are GPCRs important in medicine?
They are important targets for drug action (c.50% of all modern drugs target GPCRs)
What is the structure of enzyme linked receptors/kinase-linked receptors?
Have an extracellular ligand binding region and an intracellular catalytic domain (activated by binding) that is enzymatic in nature
Why are enzyme linked receptors/kinase-linked receptors important in medicine?
Significant interest as drug targets to treat e.g. cancers and obesity
Examples of enzyme linked receptors (4)
- Hormone (e.g. insulin)
receptors - Growth factor receptor
- Cytokine receptor
- Leptin receptor
What is Autophosphorylation?
Autophosphorylation is a type of post-translational modification of proteins. It is generally defined as the phosphorylation of the kinase by itself.
What are the target cells for insulins? (3)
- Hepatocytes
- Adipocytes
- Skeletal Muscle Cells
What is the role of insulin?
An anabolic hormone, hypoglycaemic (reduces plasma glucose)
What is the structure of the insulin receptor? How does insulin bind?
- Each receptor consists of a
ligand binding region (a-
subunit) which is linked via a
disulphide bridge to the
catalytic region (B- subunit) - A disulphide bridge then
links two of these monomers
together producing a
preformed dimer to which
insulin binds - Insulin then binds to
extracellular a-subunit this
results in
autophosphorylation of the
B-subunit - SH2 domains of IRS (insulin
receptor substrate) family
proteins binds to the
receptor
How do Intracellular Receptors act on DNA? (3)
- Influence genetic expression of enzymes
- Influence genetic expression of cytokines
- Influence genetic expression of receptor proteins
What drugs interact with intracellular receptors?
- Sex hormones
- Thyroid hormones
- Mineralocorticoids
- Vitamin D
Steroid hormones pass through the cell
membrane with ease, though transporting
them to target sites is problematic, Why?
- The inactive receptor forms a complex with HSP90
- It blocks a region called the hinge site when hormone
binds and HSP90 dissociates - The hormone-receptor complex enters the nucleus
- Entry is facilitated by a nuclear localisation signal (NLS)
that is located at the hinge site - Generally, dimerisation occurs and the hormone-
receptor complex interacts with DNA to influence gene
expression
