Video: Receptor Families

Is it true that receptors are trifunctional molecules

No - they are bifunctional

Name the 4 receptor superfamilies

• Ion channels

• G protein-coupled receptors (metabotropic receptors)

• Kinase-linked receptors

• Steroid receptors (intracellular receptors)

2 types of ion channels

Voltage gated

Ligand gated

Ion channels are important for what functions

Neurotransmission

Cardiac conduction

Muscle contraction

Secretion

When do voltage gated ion channels open

When the cell membrane is depolarised

(most important = Na+, Ca2+ & K+)

Functions of voltage gated ion channels

Control heart rhythm & constriction of blood vessels

Targets for anti-dysrhythmics (verapamil) & anti-hyperintensives (amlodipine)

Calcium channel blockers

Voltage gated sodium channels can be blocked by local anaesthetics

Ligand gated ion channels are aka

ionotropic receptors

What happens when a ligand binds to its site on the receptor

Conformational change causes the channel to open & ions to flow through

Give an example of a ligand gated ion channel receptor

Nicotinic receptor

Ligand = Acetylcholine (ACh)

Give 4 examples of ligand gated ion channel ligand

Glutamate

Acetylcholine (nicotinic)

GABA

ATP

What ions are allowed into the cell when nicotine binds to its nicotinic acetylcholine receptor

Allows Na+ & Ca2+ into the cell

Effect of nicotine binding to nicotinic acetylcholine receptor on a body system

Stimulant in the CNS - causes enhanced neurotransmitter release

In the PNS - causes the release of adrenaline from adrenal gland (fight/flight)

Nicotinic receptor is made up of how many subunits

5

Of the 5 subunits of the nicotinic receptor, how many are alpha & what is important about them

2 of the 5 are alpha subunits

They have binding sites

What receptor does GABA bind to

GABA-A receptor→ forms the GABA-A receptor complex

What ions enter when GABA binds to its receptor

Cl- ions

Hyperpolarisation

What happens when diazepam (a benzodiazepine receptor agonist) binds to the GAB-A receptor complex & GABA is also present

It opens the channel further, causing a greater hyperpolarisation

We’re onto a new receptor now!

Take a moment to compartmentalise :) 

Most abundant class of receptors

G-protein coupled receptors (metabotropic receptors)

Structure of G-protein-coupled receptors

Composed of seven transmembrane helices (heptahelical), with extracellular domain usually containing the ligand-binding region

What part of G-protein-coupled receptors activate G protein signalling molecules

Intracellular regions

Why are G proteins called as such

they bind the guanine nucleotides GTP and GDP

(G proteins = guanine nucleotide–binding proteins)

G-protein-coupled receptors activate the production of what inside the cell

Production of second messengers such as:

• cyclic AMP (cAMP)

• diacylglycerol (DAG)

• inositol 1,4,5-triphosphate (IP₃)

Give an example of a GPCR and its endogenous ligands.

β-adrenoceptors (3 subtypes, β1, β2 and β3), activated by adrenaline & noradrenaline

What is the common intracellular effect of GPCR activation?

Phosphorylation of proteins, acting as a molecular on/off switch.

Activation of β-adrenoceptors in the heart

How does activation of β-adrenoceptors in the heart affect calcium channels

It phosphorylates voltage-gated calcium channels, causing them to open, increasing Ca²⁺ influx → contracts heart muscle

What is the action of beta-blockers

They prevent β-adrenoceptor-mediated phosphorylation of calcium channels → reduced Ca²⁺ entry → decreased heart contractility.

G protein role

G protein acts as the interface between the receptor and the enzymes and/or ion channels that are the ultimate targets of GPCRs

What is the structural composition of G-proteins

They are heterotrimeric proteins with α, β, and γ subunits

What binds to the α subunit

GDP or GTP

What happens when GTP binds to the α subunit

The α subunit dissociates from the βγ complex and activates effector proteins.

What happens when GDP binds to the α subunit

It is inactive

When a G protein isn’t associated with a receptor, it has an affinity for what

GDP

Outline the sequence of GPCR activation.

1. Resting state: Receptor and G-protein not bound; α subunit has GDP.

2. Ligand binding: Ligand binds receptor → conformational change.

3. G-protein activation: Receptor associates with G-protein → GDP on α subunit replaced by GTP.

4. Subunit dissociation: α subunit with GTP dissociates from β & γ subunits.

5. Effector activation: α-GTP or βγ complex interacts with ion channels, enzymes & effector proteins.

6. Biological response: Effector activates second messengers → cell response.

7. Termination: α subunit hydrolyses GTP to GDP, reassociates with βγ, returning system to resting state.

What type of receptor is the β₂ receptor?

GPCR

What are the endogenous ligands of β₂ receptors?

Adrenaline & noradrenaline.

What is the β₂ receptor structure

crystal

We’re onto a new receptor!

Take a moment to compartmentalise!

What are kinase-linked receptors also known as

Receptors with enzymatic cytosolic domains

What is the structural organisation of kinase-linked receptors

All single membrane-spanning proteins linked to an enzyme (commonly a kinase).

How do kinase-linked receptors exert their effects

By phosphorylation or dephosphorylation of specific amino acid residues on proteins (e.g. tyrosine residues)

What biological processes are kinase-linked receptors typically involved in

Growth and differentiation.

Give an example of a kinase-linked receptor.

Insulin receptors (a member of the tyrosine kinases - the largest group)

What happens when a ligand binds to a tyrosine kinase receptor

1. Ligand binding induces receptor dimerisation & phosphorylation of tyrosine residues.

2. Phosphorylated tyrosine residues activate enzymes that phosphorylate target effector proteins in the cell → signal propagated.

What is the main metabolic effect of insulin receptor activation

Promotes glucose uptake into cells (e.g. glycogen in the liver)

How does insulin affect glycogen metabolism

Activates enzymes that synthesise glycogen.

Inactivates enzymes that break down glycogen to glucose.

We’re going onto a new receptor now!

Take a second to compartmentalise ;)

Nuclear receptors are aka

intracellular receptors

What type of ligands activate nuclear receptors

Lipid-soluble ligands (e.g., steroids) that can cross the cell membrane

Where are inactive nuclear receptors located

In the cytosol (sometimes in the nucleus).

What is the role of inactive nuclear receptors located in the cytosol

transcription regulatory factors

Describe the sequence of nuclear receptor activation

1. Lipid-soluble ligand enters cell.

2. Ligand binds to intracellular receptor.

3. Ligand-receptor complex enters the nucleus.

4. It dimerises & binds to DNA.

5. Alters transcription → alters translation of RNA

6. Altered mRNA translated into proteins → altered cell function.

Give an example of a nuclear receptor.

Steroid receptor

Why is the response to nuclear receptor activation slower compared to membrane receptors?

Because it requires transcription and translation, which take time to produce or degrade proteins.

How do steroids regulate gene expression

By activating or inhibiting transcription of specific genes

Give an example of steroid receptor action with clinical relevance.

Glucocorticoids inhibit transcription of COX-2 (cyclo-oxygenase-2), → anti-inflammatory effect.