A small ppt regarding receptors of pharmacology

1. Submitted by:
T. Sri Teja
B. Pharmacy (IV/IV)
Guided by:
P. N. Subrahmanyeswari., M.Pharm
Department of Pharmacology
Vignan Pharmacy College
Vadlamudi, Guntur (Dst), Andhra Pradesh, India ,
Pin : 522213 1

2. Contents
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S.NO Table of contents Slide Number
1. Introduction 3
2. Protein Targets for Drug Binding 4
3. Ion Channels 5-6
4. Enzymes 7-8
5. Carrier Molecules 9-10
6. Receptors 11
History 12-14
7. Drug Receptor Interactions 15
8. Classification Of receptors 16-33
9. Conclusion 34
10. References 35
11. Acknowledgement 37

3. Introduction (3)
(Targets for
drug binding)
Drug or
medicament
No therapeutic
response
Shows
therapeutic
response
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4. Protein Targets for Drug Binding (1,2)
Protein targets
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5. Ion Channels (1,2)
 Type of protein targets open only when agonist binds to receptors.
 Ex:
Benzodiazepine Tranquillizers Binds to GABA receptors
Opens chloride channel
Hyper polarisation
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6. Mechanism of opening of chloride channels
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7. Enzymes (1,3)
 Many drugs are targeted on enzymes.
Ex:
Captopril Acts on Angiotensin Converting Enzyme(ACE)
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8. Mechanism of ACE
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9. Carrier Molecules (1,3)
 These are also called Transporters.
 As cell membrane is lipophillic, it requires some carriers to facilitate
the transport of ions, organic molecules etc. across the membrane.
Ex:
Nor epinephrine Transporter(NET)
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10. Mechanism of NET
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11. Receptors (1,3)
 Receptors are the sensing elements in the system of chemical
communication that co-ordinates the function of all different cells in the
body.
 These are macro molecules.
Rece ptors
Receiving Proteins for
drugs
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12. History (1,2)
 Paul Ehrlich – 20th century
 John N. Langley- 1878, antagonism of Atropine
and pilocarpine.
 1970- Development of Receptor-labelling techniques, helped to extract and
purify the receptor material (nicotinic R).
 Extraction is done in 2 methods:
A. From electric organs of many fishes.
B. From venom of snakes of cobra family.
Extracted α-toxins
(Best is α-Bungarotoxin - Bungarus multicinctus)
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13. Postulates of Receptor Theory (2)
 A J Clark – Receptor Theory.
 Receptors must possess
Structural and steric specificity
Saturable and finite
High affinity for ligand at physiological concentrations
Early recognizable chemical event must occur
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14. Lock and Key Mechanism of Receptors
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15. Drug-Receptor Interactions (1)
 Affinity: Ability of an agent to bind with the receptors.
 Efficacy or Intrinsic Activity: Ability of an agent to activate the
receptors and produce pharmacological action.
 Agonist: Affinity + Maximum Intrinsic activity [I.A = +1]
 Antagonist: Affinity + No Intrinsic activity [I.A = 0]
 Inverse Agonist: Affinity + Negative Intrinsic activity [I .A = -1]
 Partial Agonist: Affinity + Sub max. Intrinsic activity [I.A = 0.1-0.9]
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16. Classification of receptors (1)
Based on
molecular
structure and the
nature of the
linkage
Receptor are
distinguished
into 4 super
families
Ligand-
gated ion
channels
G-protein
coupled
receptors
Kinase
linked
receptors
Nuclear
receptors
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17. Ligand-Gated Ion Channels (Ionotropic Receptors) (1,3,4)
Structure
• Pentameric Structure,
contains 2α, β, γ, δ subunits.
• 2 Acetylcholine binding
sites between interface one
of 2α subunits.
•2 α helices are present
which are responsible for
formation of gate
•Molecular weight of each
subunit is 40-58 KDa. 17
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18. Mechanism of action
Depolarisation (or) Hyper polarisation
Cellular effects
Agonist
Channel opensMovement of ions
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20. Ions
Extracellular ions
Na, Ca, Cl
Intracellular ions
K
Ions In/Efflux Response Example
Sodium Influx Stimulation Lidocaine
Calcium Influx Stimulation Nifedipine
Chloride Influx Inhibition Benzodiazepines
Potassium Efflux Inhibition Diazoxide
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Table:1

21. G-Protein Coupled Receptors (1,3,4)
 Structure:
 Single polypeptide
chain containing
Residues.
 7-Transmembrane
α- helices
 It contains:
N-Terminal Domain(Extra cellular)
C- Terminal Domain(Intra cellular)
2 agonist binding domains, 1 G-Protein binding domain
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22. G-Protein (1,3)
α+GDP & βγ Dimers
Agonist binds
Phosphorylation
GTP formation
Dimer shows action
Agonist leaves
Conversion of GTP to GDP
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23. 23Vignan Pharmacy College, Vadlamudi, Guntur, A.P.

24. Adenylate Cyclase pathway
ATP
cAMP Protein Kinase(Inactive) Protein Kinase(Active)
Lipase(IA)
ATP
ADP
Lipase (A)
Glycogen Synthase(A)
ATP
ADP
Glycogen Synthase(IA)
Phosphorylase Kinase(IA)
ATP
ADP
Phosphorylase Kinase(A)
Phosphorylase b(IA)
ATP
ADP
Phosphorylase a(A)
Reduced Glycogen
synthesis
Increased
Lipolysis
Glycogen moieties(IA)
ATP
ADP
Glucose-1-phosphate
Increased glycogen breakdown
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Phosphodiesterase
Adenylate
Cyclase

25. Phospholipase C Pathway (1)
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26. Location Receptor Shows Action
on
Inhibition/
Stimulation
Pharmacological
Action
Cardiac
Muscle
Gs Adenylate
Cyclase
Stimulation Increase Cardiac
output
Bronchi Gs Adenylate
Cyclase
Stimulation Relaxation &
bronchodilation
Heart Gi Adenylate
Cyclase
Inhibition Decrease force of
contraction
Uterus Gi Adenylate
Cyclase
Inhibition Contraction
Glands Gq Phospholipase C Stimulation Increase Secretions
Small
Intestine
Gq Phospholipase C Stimulation Contraction
(Motility of S.I)
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27. Kinase Linked Receptors (or) Enzymatic Receptors (1)
Structure:
 Possess a single chain of 1000 residues
 Extracellular N-terminal, Intracellular C-terminal
 Here the receptors are coupled to enzymes.
 These receptors are mainly helpful in Cellular growth, cell division, etc.
Types of Enzymatic receptors:
A. Receptor tyrosine Kinase
B. Serine/ Threonine Kinase
C. Cytokine Receptor
D. Guanylyl- Cyclase Kinase
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28. Seven subfamilies of receptor tyrosine Kinase
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29. Mechanism of receptor Tyrosine Pathway (1)
1) Binding of Ligand
2) Dimerisation
of reseptor
-OH -OH -OHTyr kinase
domain
(Janus kinase)
Phosphoryl of Tyr
O P O P
STATS
protein
O P O P STATS
protein 1) Phosphoryl. of STAT
2) Release of STAT in cytoplasma
3) STATto cell nucleus
4) Intitation of transcription
Ras
GDP
GTP
Ref
P
Mek
P
Map Kinase
P
Various Transcription
factors
P
Gene Transcription
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30. Mechanism of Cytokine Receptors (JAK/STAT Pathway) (1)
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31. Nuclear Receptors (3)
Structure:
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• Intracellular Receptors
• Transcription Factors
transduce the signals
by modifying
Gene Transcription

32. Mechanism of Action
Ligand binds to receptor
Change in Gene Expression
Synthesis of Specific Protein by mRNA
Shows Pharmacological Action
Stimulatory Inhibitory
Based on type of protein Synthesized
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33. Name of the Receptors Examples
Ligand Gated Ion Channels Nicotinic AcH Receptors
GABA Receptors
NMDA Type of glutamate Receptors
G- Protein Coupled
Receptors
Muscarnic AcH Receptors
Adreno Receptors
Opiate Receptors
Kinase Linked Receptors Growth Factors
Cytokines
Hormones like Insulin, Leptin
Nuclear Receptors Steroidal Receptors
Aldosterone Receptors
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34. Conclusion
 Extensive research done on receptor pharmacology lead to discovery
of new drug targets for treatment of several diseases.
 Still requires discovery of new receptor types and mechanism of
many orphan receptors that can result in effective treatment of many
diseases.
 Requires development of receptor crystallization.
 Must to be discovered about the nuclear receptors.
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35. References:
 Rang and Dale; Pharmacology; Pg.no: 20-22, 24-52
 Dr. S. S. Kadam; Principles of Medicinal Chemistry; Pg.no: 43-44
 KD. Tripathi; Essentials Of Medical Pharmacology; Pg.no: 37-60
 Wilson And Griswold; Text Book of Organic, Medicinal And
Pharmaceutical Chemistry pg.no; 524-545, 548-580
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36. Vignan Pharmacy College, Vadlamudi, Guntur, A.P.
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ANY QUIRIES ?????

37. Vignan Pharmacy College, Vadlamudi, Guntur dist. A.P. 37
 I would like to express my gratitude to all those who gave me the
possibility to complete this seminar .
 I express my sincere gratitude to my guide P.N.Subrahmanyeswari
madam, who suggested with great patience.
 A special thanks to the Principal sir, Dr. P. Srinivasa Babu garu
and special thanks to Sowjanya madam and seminar committee
whose encouragement contributed immensely to complete my
seminar.

38. Vignan Pharmacy College, Vadlamudi, Guntur, A.P.
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