2. Content
Introduction to receptors
Classification of receptors
Introduction to GPCR faimily
Example of GPCR
Structural feactures of GPCR
Signal transduction pathway
3. Introduction to Receptors
Receptors are the protein structure, which binds drug,
hormone or neurotransmitters to produce biological
action.
LOCATION:- Mostly receptors are present on the cell
membrane and some are present in cytoplasm and
nucleus
LIGAND:- The molecules which binds to receptors called
Ligand. Example Drugs, hormones and neurotransmitters
Latin word Ligare Means “To bind”
4. Introduction to receptors
Type of Ligands
1. Agonist A chemical substances that bind and activate
the receptors to produce a biological action
2. Partial agonist They are agonist that bind and activate
a given receptor but have only partial efficacy at the
receptor relative to full agonist
5. Introduction to receptor
3.Antagonist are the substance that bind and block the
receptor rather than activating it like agonist.
They interfere in natural operation of receptor
(a) Competitive antagonist compete with agonist to bind with
same receptor. They may be reversible or irreversible
(b) Non competitive antagonist They bind to an allosteric site on
the receptor to prevent action of agonist
4 Inverse agonist they binds to same receptor as agonist but
induce a pharmacological action opposite to that of agonist
7. Classification of receptor family
Receptors has been classified into different type
depending on structure and function
1. Present on cell membrane
(a) G protein coupled receptor
(b) Ligand gated ion channel
(c)Receptor tyrosine kinase
2. Present inside cytoplasm
(a)Nuclear receptor
9. G Protein coupled receptor
GPCR is the largest family of cell surface receptor.
About one third of currently available drug acts by binding to
GPCR.
HPCR are responsible for every aspect of human biology from
taste ,vision ,smell,sympathetic and parasympathetic nervous
system ,metabolism and immune system
The name “G-protein coupled receptor” is because these
receptors are coupled with G- protein.
G- protein is Guanine nucleotide (GTP/GDP) binding protein.
12. Structural features of GPCR
All type of GPCR receptors have seven trans – membrane domain ,
connected by three extracellular loops and three Intracellularloops.
So, they are also called 7-Transmembrane helical receptor or
“Surpentine receptors”.
The extracallular region of GPCR posseses N- terminus (NH2) and
binding site.
The intracellularregion of GPCR posseses C- terminus (-CooH) and
interacts G- protein.
Due to binding of G- protein these receptors are called “ G- protein
coupled Receptors.
G- protein are composed of 3 different Subunits ------ α, β and γ
13. Type of G proteins
Since most of the well known function are performed by binding of
Alpha - subunit of G- protein with an effector.
So, on the basis of Alpha – subunit , there are different type of G-
Protein.
G- protein are grouped into 4 faimily
1.Gαi --- Largest & most diverse faimily
i → stand for inhibition of Adenylyl cyclase then increase level of
. cAMP and leads to opening of k+ channels.
2. Gs → Two members in this faimily Gs and G olf
S→ stand for stimulation of Adenylyl cyclase and increase cAMP .
. level and opening of Ca++ channels
Olf – stands for olfactory
3. Gαo→ Inhibition of Ca++ channels.
4. Gαq- phospholipase C activation.
16. Signal transduction process
The different steps involved in signal transduction during activation of G
protein couple receptors include the following—
1. In normal resting state i.e. In the absence of any stimulus/ligand,
guanosine diphosphate (GDP) is bound to the oc-subunit of the G
proteins.
2. Upon activation of receptors by binding of a ligand, there is a
conformational change in Gproteins and GDP dissociates from
oc-β-γ subunit
3. In the meanwhile, GTP associates with the oc-subunit of the G
proteins. In other words ligand binding leads to exchange of
GDP with GTP.
4. The binding of GTP activates the oc-subunit and subsequently,
cx-GTP subunit dissociates from β and γ subunits.
17. Signal transduction process
5. The free oc-GTP subunit binds to the effector/target protein and
modulates its activity depending on the type of G proteins. Gs
stimulates adenylyl cyclase to increase cAMP,opens Ca2+ channels; Gi
inhibits adenylyl cyclase to decrease cAMP, opens K+ channels; Go
inhibits Ca2+ channels; Gq regulates phospholipase-C activity.
6. Due to intrinsic GTPase activity of oc-subunit, GTP is hydrolyzed
to GDP and the resulting oc-GDP complex dissociates from the
effector.
7. The oc-GDP complex reassociates with the β-γ subunit to
complete the cycle. It brings the cell back to normal resting
state.
18. G protein coupled effector system
There are 3 main G protein coupled effector system including adenylate cyclase,
phospholipase C and ion channels
1. Adenylate cyclase: It is a transmembrane enzyme and important effector system. It
has been linked with Gs and Gi protein
Binding of norepenephrine on beta adrenergic receptor in heart
Activation of Gs protein of beta adrenergic receptor
Activation of adenylate cyclase {AC}
Increase cAMP level
Activation of protien kinase A
Opening of ca++ chanells and increase intracellular ca++ level
Increase heart contractility and heart rate
19. G protein coupled effector system
Activation of Gi protein of muscarinic receptor
Inhibition of adenylate cyclase {AC}
decrease cAMP level
Decrease intracellularca++ level
decrease heart contractility and heart rate
21. G protein coupled effector system
2. Phospholipase C It is a membrane linked enzyme
Activation of Gq linked GPCR receptor
Activation of phospholpase C {PLC} enzyme
PLC acts on phospatidyl inositol 4,5 biphosphate [PIP2]
Generation of inositol triphosphate [IP3] and Diacyle glycerol [DAG}
Release of ca++ from endoplasmic reticulam
Physiological action
23. G protein coupled effector system
3. Ion channels
In addition to α subunit, β subunit of G protein ,may also modulate the functioning of
effector.
The most common target for G β-γ subunit is GIRKs {G protien regulated inwardly
rectifying K+ Channel ]
GIRKs cause inward movement of K+ ions
Other targets of G β-γ subunit is Q and N type voltage gated ca++ chanels
