Types of Receptors
1) Ionotropic Receptor
Extracellular face (ligand binds on
the extracellular face on only the
α-subunit).
2) Tyrosine Kinase Receptor
[TKR] or (Tyrosine-Linked
Receptor)
Binding domain is on the
extracellular face, and facing the
cytoplasmic region is the catalytic
domain.
3) Nuclear Receptor (Cytosolic
Description
They are also called receptor operated channels (Ligand
gated ion channels). It has two ligand binding sites and
has to be both occupied for the channel to open (gets
activated).
Main ligands:
Ach, GABA, glutamate.
Time Scale:
Milliseconds→ Important for the nervous system and
Ach is responsible for synaptic transmission.
Effector:
Ion channel.
Structure:
Oligomeric (5 different subunits, 2α- where they have
binding sites and one from β, γ, and δ sites).
Mode of action:
Direct coupling, neurotransmitter act on the
postsynaptic membrane of the nerve or muscle.
Increasing permeability to Na+ or K+ channel, this
depolarizes the cell and we get action potential→ muscle
contraction.
Change at molecular level has caused a systematic
change.
MCQ: Know the ligands, know GABA and which type of
receptor is used, hormones such as steroid hormones for
nuclear receptor and insulin for tyrosine receptors.
It mediates the action of protein mediators such as
growth factors, cytokines and hormones.
Main ligands:
- Insulin, Growth Factors and Cytokines.
Time Scale:
- Few hours.
Effector:
- Enzymes.
Structure:
Has only one transmembrane that spans the lipid
bilayer. Has a very large extracellular domain linked by
sulphide bonds. Cytoplasmic face has tyrosine residue
that’s why it is called tyrosine kinase.
Mode of action:
Agonist binding gets dimerization of receptor→ both are
linked, phosphorylation at tyrosine residue and that is
cross phosphorylation.
Phosphorylated tyrosine acts as a receptor for SH2 (Src
Homology 2) domain of proteins. Example of SH2
domain is (GRB2) → SH2 domains get phosphorylated
and allows recruitment of other protein ligands passed.
Example:
Growth Factor attachment to Ras pathway.
Cytokine attachment to Jak pathway.
Regulates DNA transcription.
 Receptors)
4) G-Protein Coupled Receptor
(Metabotropic Receptor)
7 transmembrane spanning across
the lipid bilayer, the binding
domain is on the ECF and the
coupling domain is on the CPD.
Main Ligands:
Steroids and thyroid hormones.
Time Scale:
Few hours/hours/days.
Effector:
Gene transcription.
Structure:
Ligands are lipophilic that can diffuse through the
membrane and attach to DNA binding domain. The DNA
binding domain has two Zn (zinc) fingers and four
cysteine residues.
Mode of action:
Steroids→ binds to receptor which causes a
conformational change of receptor. Receptor
dimerizes→ This receptor binds specific DNA sequence
upstream of the gene called HRE (Hormone Response
Element).
Different hormones activate or supress different genes
ex: glucocorticoids inhibit COX2→ anti-inflammatory.
Mineralocorticoids stimulate production of transport
protein so this is important in renal tubular function.
G-Protein is an indirect coupling, the word coupling
refers to the region where the action occurs. G-Protein
sends a secondary messenger.
Main Ligands:
Muscarinic Ach (Easy way to remember this ligand is
Metabotropic is for Muscarinic, the letter M).
Adenoreceptors.
Chemochine Receptors.
Time Scale:
Seconds.
Effectors:
Coupled through G-Proteins.
→ The effect is on the enzyme or an ion channel.
Mode of action:
Indirect coupling, G-Protein + 3 subunits which are: α-
subunit and βγ complex which are linked together.
At resting state: α subunit binds to GDP forming α-GDP
and leaves the βγ complex, when ligand binds the
receptor; it gets a conformational change from α-GDP →
α-GTP.
α-GTP binds to target and α-GTP gets converted to α-
GDP and it binds to the βγ complex again.
Important:
Muscarinic Ach and Adenoreceptors both work on
cardiac muscle and both work on the same protein,
however opposite effects is observed. Why?
G-proteins come in different types, G s is stimulatory and
Gi is inhibitory. Thus, there are subtypes of G-protein.
Three different targets for G-protein:
1) Adenylate Cyclase:
 It converts ATP to cAMP, and the reverse
reaction is also possible to give 5’-ATP which is
catalysed by the enzyme phosphodiesterase.
GPCR increases adenylate cyclase activity in
order to make more cAMP.
cAMP activates protein kinase A (kinase is a class
of enzyme that transfers a phosphate group
from ATP to ADP, no matter what the substrate
is being used. Phosphorylation adds phosphate,
no transfer occurs).
Kinase phosphorylates serine and threonine
which activates or inhibits the enzyme.
It regulates the enzyme during metabolism. It
also regulate cell division and differentiation.
2) Phospholipase C and Inositol System:
PIP2 is a substrate for phospholipase Cβ enzyme
(PLCβ).
PLCβ splits PIP2 into:
- IP3: Binds to receptors in the endoplasmic
reticulum and increases calcium
permeability.
- DAG: Activates protein kinase C, it
phosphorylates intracellular proteins.
Protein kinase C is activated by high levels of
Ca2+ ions.
Difference: DAG is lipophilic which doesn’t
diffuse and stays on the membrane. IP3 diffuses
as a secondary messenger into the membrane.
3) Ion Channels target:
Controlled without a secondary messenger
system, which uses direct link from the channel.
Muscarinic Ach increases K+ permeability and
causes hyperpolarization which inhibits electrical
activity.
Module 1- Fundamentals of Biomedicine

FUN8 and 10: Receptors (Pharmacology)