1. PHL 210 Pharmacology
Second Lecture By Abdelkader Ashour, Ph.D. Phone:

2. Drug Receptors
Receptor/Binding site
“A specific protein in either the plasma membrane or interior of a target cell with which a ligand/drug combines”
It must be selective in choosing ligands to bind  To avoid constant activation of the receptor by promiscuous binding of many different ligands
It must change its function upon binding in such a way that the function of the biologic system (cell, tissue, etc) is altered  This is necessary for the ligand to cause a pharmacologic effect

3. Drug Receptors
Receptor/Binding site
“A specific protein in either the plasma membrane or interior of a target cell with which a ligand/drug combines”
It must be selective in choosing ligands/drugs to bind  To avoid constant activation of the receptor by promiscuous binding of many different ligands
It must change its function upon binding in such a way that the function of the biologic system (cell, tissue, etc) is altered  This is necessary for the ligand to cause a pharmacologic effect

4. Drug Receptors
Receptor/Binding site
“A specific protein in either the plasma membrane or interior of a target cell with which a ligand/drug combines”
It must be selective in choosing ligands/drugs to bind  To avoid constant activation of the receptor by promiscuous binding of many different ligands
It must change its function upon binding in such a way that the function of the biologic system (cell, tissue, etc) is altered  This is necessary for the ligand to cause a pharmacologic effect
Drug
In order to interact chemically with its receptor, a drug molecule must have the appropriate size, electrical charge, shape, and atomic composition
Orphan receptors
“Receptors for which no ligand has been discovered but they have a similar structure to other identified receptors and whose function can only be presumed”
If a ligand for an orphan receptor is later discovered, the receptor is referred to as "adopted orphan receptor"

5. Drug Receptors, contd. Receptor Down-regulation Desensitization
“A decrease in the total number of target-cell receptors for a given messenger/ligand in response to chronic high extracellular concentration of the messenger/ligand”
Desensitization
“The loss of a drug’s effect, when it is given continuously or repeatedly, on a short time-scale”
Often results from receptor down-regulation
Receptor Up-regulation
“An increase in the total number of target-cell receptors for a given messenger/ligand in response to a chronic low extracellular concentration of the messenger/ligand”
Supersensitivity
“The increased responsiveness of a target cell to a given messenger/ligand, resulting from receptor up-regulation”

6. Drug Receptor Interactions
Agonist
“A chemical messenger (or drug) that binds to a receptor and triggers the cell’s response; often refers to a drug that mimics a normal messenger’s action”.
For example, pilocarpine is a muscarinic receptor agonist because it can bind to and activate muscarinic receptors
Antagonist
"A molecule that competes for a receptor with a chemical messenger normally present in the body. The antagonist binds to the receptor but does not trigger the cell’s response”
For Example, atropine is a muscarinic receptor antagonist because it can bind to muscarinic receptors but it does not trigger the cell’s response. In this way, it prevents binding of acetylcholine (ACh) and similar agonist drugs to the ACh receptor

7. The Lock and Key Model of Signal-Receptor Interaction
Drug Receptor Interactions
The Lock and Key Model of Signal-Receptor Interaction
Ligands such as hormones, neurotransmitters or drugs (the "key") affect target cells by binding to specific receptors (the "lock”), which are often located in the cell membrane
This binding "unlocks" the cell's response, so that the hormone or neurotransmitter can exert its effects

8. Drug Receptor Interactions
Lock and key mechanism
Agonist
Receptor
Agonist-Receptor
Interaction

9. Drug Receptor Interactions
Competitive
Inhibition
Antagonist
Receptor
Antagonist-Receptor
Complex
DENIED!

10. Drug Receptor Interactions
Non-competitive
Inhibition
Antagonist
Agonist
Receptor
DENIED!
‘Inhibited’-Receptor

11. Drug Receptor Interactions, contd.
Affinity
The extent to which the ligand/drug is capable of binding and remained bound to receptor
High Affinity – the ligand binds well and remains bound long enough to activate the receptor
Low Affinity – the ligand binds less well and may not remain bound long enough to activate the receptor
High Affinity

12. Drug Receptor Interactions, contd.
Affinity
The extent to which the ligand/drug is capable of binding and remained bound to receptor.
High Affinity – the ligand binds well and remains bound long enough to activate the receptor
Low Affinity – the ligand binds less well and may not remain bound long enough to activate the receptor
Low Affinity