Receptors are proteins that receive chemical signals from outside the cell. When a ligand binds to a receptor, it causes a cellular response. There are several types of receptors including ion channel linked receptors, G-protein linked receptors, enzyme linked receptors, and nuclear receptors. Nuclear receptors are located within cells and bind lipophilic ligands like steroids and lipids to regulate gene expression. [/SUMMARY]

1.  BY : FOZIYA KHAN
 PHARMACOLOGY BRANCH
 SEM I

2.  INTRODUCTION
 CHARACTERISTICS
 CLASSIFICATION
 ION CHANNEL LINKED RECEPTORS
 G- PROTEIN LINKED RECEPTORS
 ENZYME LINKED RECEPTORS
 NUCLEAR RECEPTORS

3. What is receptor?
 A receptor is a protein molecule usually found inside or
on the surface of a cell that receives chemical signals
from outside the cell.
 When such chemical signals bind to a receptor, they
cause some form of cellular/tissue response, e.g. change
in the electrical activity of cell.
 Therefore, a receptor is a protein molecule that
recognizes and responds to endogenous chemical signals,
e.g. the acetylcholine receptor recognised and responds
to its endogenous ligand, acetylcholine.

4. 1. Participates in transduction of the signal
from the external messenger to some
component of the metabolic pathway.
2. Has atleast one additional functional site
which is altered by ligand binding (allosteric
site).
3. Ligand binding to receptors is saturable,
resembling Michaelis – Menten kinetics.

5. INTRA-CELLULAR
RECEPTORS
CELL SURFACE
RECEPTORS
NUCLEAR
RECEPTORS

6. ION CHANNEL LINKED RECEPTORS
G- PROTEIN LINKED RECEPTORS
ENZYME LINKED RECEPTORS

7.  Act through synaptic signaling on electrically
excitable cells and convert chemical signals (ligands) to
electrical ones.
 These membrane spanning proteins undergo a
conformational change when a ligand binds to them.
 These ligands can be neurotransmitter, peptide
hormones and the molecule that pass through are ions
such as sodium or potassium ions which can alter the
charge across the membrane.
 The ion channel, or pores are opened only for a short
time, after which the ligand dissociates from the
receptor and the receptor is available once again for a
new ligand to bind.

9.  Also called as
1. Seven- (pass) transmembrane domain
receptor i.e. 7TM Receptors because they pass
through the cell membrane seven times.
2. Heptahelical receptors
3. Serpentine receptors
4. G- Protein linked receptors
 GPCRs associate with heterotrimeric G-
Proteins (green), i.e. G- Protein composed of 3
different subunits: α, β and γ.

10.  GPCR located in cell membrane binds extracellular
substances and transmits signals from these substances
to an intracellular molecule called a G- Protein (Guanine
nucleotide binding protein).
Example:β- adrenergic receptors which bind
Epinephrine.
Prostaglandin E2 receptors which bind
inflammatory substances called Prostaglandin and
Rhodopsin which contains a photo reactive chemical
called retinal that respond to the light signals received
by rod cells in eye.
 There are 2 principal signal transduction pathway
involving G- Protein linked receptors:
1) CAMP Signal Pathway
2) Phosphatidylinositol Signal Pathway

12.  Also known as a catalytic receptors
 transmembrane receptor, where the binding
of an extracellular ligand causes enzymatic
activity on the intracellular side.
 integral membrane protein possessing both
enzymatic catalytic and receptor functions.
 Upon ligand binding a conformational change
is transmitted which activates the enzyme,
initiating signaling cascades.

13. 1) Receptor Tyrosine Kinase (RTK): contains intrinsic
tyrosine kinase activity (EGFR, VEGFR)
2) Receptor Serine/ Threonine Kinase: contains intrinsic
serine / threonine kinase activity (TGF- βR)
3) Receptor Guanylyl Cyclases: contain intrinsic cyclase
activity (ANP)
4) Tyrosine- Kinase associated Receptors: receptors that
associate with proteins that have tyrosine kinase activity
(Cytokine receptors)
5) Receptor Tyrosine Phosphatases
6) Histidine- Kinase associated Receptor

15.  RTK ligands, such as fibroblast growth factor (FGF),
epidermal growth factor (EGF), nerve growth factor (NGF)
etc. bind as dimers.
 Ligand binding to RTK monomers results in dimer
formation.
 Receptors possess an intracellular tyrosine kinase
domain. Within the dimer the conformation is changed,
locking the kinase into an active state.
 The kinase of one receptor then phosphorylates a
tyrosine residue contained in the “activation lip” of the
second receptor.

16. This forces the activation lip out of the kinase
active site, allowing ATP bind and resulting in
enhanced kinase activity.
 This induces phosphorylation at further tyrosine
residues.
 Phosphotyrosine Is a conserved “docking site”
for many intracellular signal transduction proteins
that contain SH2 domains.

17.  Nuclear receptors are a family of highly conserved
transcription in response to small lipophilic compound.
 Play important role in development, physiology and
diseases in humans by regulating gene expression (Protein
and Amino acid formation)
 Estrogen or β- estradiol act upon the nuclear receptor to
regulate gene expression for Female Sex Development.
 Testosterone or Androgens act upon nuclear receptors to
regulate gene expression for Male Sex Development.

19.  N- terminal domain: harbors AF1 site that binds to
other cell specific transcription factors in a ligand-
independent way and modifies the binding or activity of
the receptor
 DNA binding domain: Binds to the specific sequences
of DNA called hormone response element
 Hinge region: Connects the DNA binding domain to
the ligand binding domain
 Ligand binding domain: Harbors the AF2 whose action
depends upon the bound ligand
 C- terminal domain: has ability to the transcription

20.  CLASS I NUCLEAR RECEPTORS:
> Largely steroid receptors
> Ligands are mainly steroids
> Located in cytoplasm or attached to
cytoskeleton or other structures
> When ligand binds, form homodimers
in the presence of their partners and migrate to
nucleus to trigger signal response
> A single ligand can regulate a large
number of genes

21.  CLASS II NUCLEAR RECEPTORS:
> Their ligands are mainly lipids
> Located in nucleus
> They form heterodimers with
retinoid X receptors
 CLASS III NUCLEAR RECEPTORS:
> They transduce endocrine signals but
function as homodimers