This document provides information about a receptor pharmacology course taught by Professor Dr. Md. Shah Amran at the University of Dhaka. It was prepared by 5 students and contains an introduction to receptors, classifications of different receptor types including ligand gated ion channels, G-protein coupled receptors, enzyme linked receptors, and nuclear receptors. It also discusses receptor-drug interactions, affinity, intrinsic activity, and mechanisms of cell surface and intracellular receptors.

1. Receptor
Course faculty:
Professor Dr. Md. Shah Amran.
Faculty of Pharmacy ,University of Dhaka
Guest faculty of Department of pharmaceutical sciences
North South University

2. PREPAERD BY
Atiqur Rahman Nyeem -1320819046
Md Samrul Islam -1321111046
Nusrat Jahan Khan - 1321022646
Fatama Shoulin Taluckder-132111846
Faria Iqbal -132

3. CONTENTS
 Introduction - receptor
 Drug – receptor interactions
 Ligand gated ion channel receptors
 G – protein coupled receptors
 Enzyme liked receptors
 Nuclear receptors
 Comparison of receptor types
 Conclusion
 References

4. What Is A Receptor?
Definition : Receptors are macromolecules ,
composed of lipoprotein . They are located on the
cell membrane or inside the cell ( either in
cytoplasm or nucleus).
 Receptor bind with drug and form drug- receptor
complex. The magnitude of the response is proportional
to the number of drug–receptor complexes:
 The receptor not only has the ability to recognize a
ligand, but can also couple or transduce this binding
into a response by causing a conformational change
)(Re/)(Re)( sponseComplexRDRceptorDDrug Kd


6. o Affinity
The capability of a drug to form the complex (Drug-Receptor Complex) with its
receptor.
o Intrinsic activity
The ability of a drug to trigger the pharmacological response after making the
drug-receptor complex.
D+R —> DR
D: Drug or endogenous ligand
R: Receptor
DR: Drug-Receptor Complex

7. Based on affinity and intrinsic activity :
 Full agonist : high affinity
high intrinsic activity(=1)
Eg. Methacholine on acetylcholine receptors
 Antagonist : only affinity
no intrinsic activity (=0)
Eg. Atropine on muscarinic receptors

9. Classification of receptor
1)Cell-surface receptor : located on the cell membrane
e.g.
1. ion channel-linked receptors/ ligand gated receptor
2. G-protein-couple receptors,
3. And enzyme – linked receptor ( tyrosine kinase receptor )
2) Intracellular receptor : located on the cytoplasm
e.g. steroid receptor
3) Nuclear receptor : located in the nucleus of the cell.
e.g. thyroid receptor .

10. Ligand Gated Ion Channels
 Also called ionotropic receptors.
 They are responsible for regulation of the flow of ions across cell
membrane
 Involved mainly in fast synaptic transmission.
Eg: nAchR, GABAA, and glutamate receptors of the NMDA, AMPA and
kainate types.

11. 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.
Ligand
binding site

12. Mechanism of action of
Ligand Gated Ion Channel receptor

13. Ion channels - importance
 Generation , propagation of nerve impulse.
 Synaptic transmission of neurons.
 Muscle contraction.
 Salt balance.
 Hormone release.
 Muscle relaxants , anti-arrhythmatics ,anesthetics – act by blocking ion channels.

14. G-Protein Coupled Receptors
• G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein.
• All G-protein-linked receptors have seven transmembrane domains, each has its own specific
extracellular domain
• E.g. adrenoceptors, dopamine, 5-HT, opiate, peptide, purinoceptors, orphans
• signaling molecule bind with extra cellular domain of receptor , conformational change occur.
• GDP in G- protein is replaced by GTP , which activate G-protein .
• G-protein – GTP complex dissociate from the receptor and activate one of this two pathway
 1st pathway – adenylyl cyclase pathway (ALC)
 2nd pathway - PLC pathway

15. Two Pathway

16. Adenylyl Cyclase System
 cAmp-nucleotide synthesized from ATP-by adenylyl cyclase,metabolized by
PDE
 Regulate enzymes of metabolism,growth,contractile proteins of muscle
 NT-acts on GPCR-Gs/Gi activated –produce effects –by increasing or
decreasing activity of adenylyl cyclase and cAMP
 cAMP-activate-Protein kinases-activate/inactivate enzymes by
phosphorylation-cellular events.

18. Phospholipase C-Inositol System
 Phospholipase C: Celaves membrane phospholipids-phosphoinositides
 PLC beta-cleaves phosphatidylinositol(4,5) bis Phosphae PIP2 into DAG and
IP3
 DAG and IP3-Secondary messengers-elicit cellular response

20. 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.

21. G-PROTEIN RECEPTOR FOR SIGNALLING PATHWAY
GS Beta adrenergic amines,
glucagon histamine, serotonin
Adenylyl cyclase
CAMP
•Excitatory effects
Gi1, Gi2, Gi3 Alpha2 adrenergic amines,
mAchR, opioid,
serotonin
adenylyl cyclase
CAMP
Cardiac K+ channel open-
heart rate
Golf Olfactory epithelium Adenylyl cyclase –
CAMP21

22. G-PROTEIN RECEPTOR FOR SIGNALLING PATHWAY
GO NT ,Opioid
cannabinoid
Not clear
Gq mAchR, serotonin 5HT1C PLC
IP3 , DAG
Cytoplasmic Ca
Gt1 , Gt2 Rhodopsin and colour
opsins in retinal rod and
cone cells
cGMP
phosphodiesterase- cGMP
22

23. ENZYME LINKED RECEPTORS
 Ligand binds to the extracellular domain of kinase linked receptor , a signal
is transferred through the membrane and activates the enzyme, which sets
off a chain of events within the cell that eventually leads to a response.
 The most common enzyme-linked receptors are those that have a
tyrosine kinase activity as part of their structure.
Example :epidermal growth factor,
platelet-derived growth factor
atrial natriuretic peptide
insulin
 They have large extracellular and intracellular domains, but the
membrane-spanning region consists of a single alpha-helical region of
the peptide strand.23

24. MECHANISM OF ENZYME LINKED RECEPTOR

25. INTRACELLULAR RECEPTORS
Ligand activated transcription factors.
Present in soluble form – either in cytoplasm or nucleus – freely diffusible.
Transduce signals by- modifying gene transcription.
Eg: steroid hormones, glucocorticoids, vit D and A, orphan receptors
Play vital role in endocrine signaling and metabolic regulation.
25

27. Several diseases are result from alteration in receptors and their
immediate signaling effectors . This principle mechanism involved are :
 Autoantibodies directed against receptor proteins
 Mutation of gene encoding receptors and protein involving receptors
Malfunctioning of receptors

28. Receptor diseases
Parkinson’s disease: Higher than normal density of dopamine receptors is found
in the putamen and caudate nucleus
Hyperkplexia: Decreased affinity of glycine for the glycine receptor, due to a
mutation in the glycine receptor
Myasthenia gravis : Where circulating antibodies against acetylcholine receptors
decrease the number of receptors at the neuromuscular junction

29.  Desensitization of receptors : A gradual decrease in the effect of a drug on continued or
repeated administration
2 types:
1) Homologous desensitization : in which agonist desensitize the same receptor they activate.
2) Heterologous desensitize: In which agonist can desensitize other receptors
 Hypersensitivity of receptors : This indicates an increase in the activity of receptors.
• This results rom prolonged suppression of receptor stimulation
• E.g. propranolol
Physiological effect of receptors

30. 30

31. 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 the mechanisms of many
orphan receptors that can result in effective treatment of many diseases.
 Requires development of receptor crystallization etc.
 Much to be discovered about the nuclear receptors.RECEPTORS @ VPC31