biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems
2. Receptor
A receptor is a protein molecule usually found embedded
within the plasma membrane surface of a cell that
receives chemical signals from outside the cell and when
such chemical signals bind to a receptor, they cause some
form of cellular/tissue response.
3. WHAT IS ARECEPTOR?
•Specialized areas of cell to which drugs get bound.
•They are regulatory protein macro molecules .
•Drug should have –selectivity to a receptor ;
receptor should have ligand specificity to elicit
action.
5. Classification
There are 2 types of receptors. Those are : Internal &
Cell surface receptor.
i. Internal /Intracellular/Cytoplasmic receptors :
found in the cytoplasm of the cell
respond to hydrophobic ligand molecules
6. Internal receptor :
Internal /Intracellular Receptors :
Hydrophobic signaling molecules typically diffuse
across the plasma membrane
interact with intracellular receptors in the cytoplasm.
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7.
8. Cell surface receptor
ii. Cell-surface /transmembrane receptors/cell-
specific proteins
performs signal transduction, converting an
extracellular signal into an intracellular signal.
3 main components:
i. External ligand-binding domain (extracellular
domain)
ii. Hydrophobic membrane-spanning region
iii. Intracellular domain inside the cell
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9. Cell surface receptor
There are three general categories of cell-surface
receptors:
• Inotropic.
Ion channel-linked receptors,
Ligand gated ion channel
Direct alter membrane potential
• Metabotropic
G-protein-linked receptors,
Enzyme-linked receptors.
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12. Ion Channel-Linked Receptors
Receptors bind with ligand. (Ex:Nicotinic Receptor)
Open a channel through the membrane that allows
specific ions to pass through.
Conformational change in the protein's structure that
allows ions such as Na,Ca, Mg, and H2 to pass through.
13. ION CHANNELS - IMPORTANCE
• Generation , propagation of nerveimpulse.
• Synaptic transmission ofneurons.
• Muscle contraction.
• Salt balance.
• Hormone release.
• Muscle relaxants , anti-arrhythmatics ,anesthetics – act
by blocking ion channels.
14. MOLECULAR STRUCTURE
•ligand binding site in extracellular domain.
•4 subunits α, β, γ and δ.
•α2, β, γ - pentameric str - 2 ligand binding sites
•Each subunit spans the membrane 4 times; all
subunits form a central pore.
22. G-Protein Linked Receptors
Binds with a ligand and activate a membrane protein
called a G-protein.
The activated G-protein then interacts with either an ion
channel or an enzyme in the membrane.
Each receptor has its own specific extracellular domain
and G-protein-binding site.
Example : Beta-adrenergic receptor
23. metabotropic or 7-transmembrane-spanning (heptahelical) receptors.
coupled to intracellular effector systems via a G-protein.
mAChRs, adrenoceptors, dopamine, 5-HT, opiate, peptide,
purinoceptors, orphans .
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25. FAMILIES OF GPCR
3 families:
A – rhodopsin family
eg. Amine NT, purines , cannabinoids
B - secretin/glucagon receptor family Eg. Peptide hormones.
C - metabotropic glutamate receptor/calcium sensor family.
Eg. GABAB, Glutamate.
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26. G-PROTEIN -ROLE
Membrane resident proteins – recognize activated GPCRs- pass message to
effector system.
Occurs in interaction with guanine nucleotides ; freely moving in cytoplas
α, β and γ subunits – trimer in resting state.
3 subunits attached to GPCR through fatty acid chain – reaction called
prenylation.
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27. Enzyme-Linked Receptors
Cell surface receptors with intracellular domains that are
associated with an enzyme.
Normally have large extracellular and intracellular
domains.
When a ligand binds to the extracellular domain, a signal
is transferred through the membrane and activates the
enzyme, which eventually leads to a response.
Example : Tyrosine Kinase receptor