PHL 211 Pharmacology

Second Lecture

By

Abdelkader Ashour, Ph.D. Phone: 4677212 Email: aeashour@ksu.edu.sa

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

Drug Receptors

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 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

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"

In order to interact chemically with its receptor, a drug molecule must have the appropriate size, electrical charge, shape, and atomic composition

Receptor Down-regulation“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”

Drug Receptors, contd.

Supersensitivity“The increased responsiveness of a target cell to a given messenger/ligand, resulting from receptor up-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”

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

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

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

Drug Receptor Interactions

Drug Receptor Interactions

Agonist Receptor

Agonist-Receptor

Interaction

Lock and key mechanism

Antagonist Receptor

Antagonist-Receptor

ComplexDENIED!

CompetitiveInhibition

Receptors.exe

Drug Receptor Interactions

Agonist Receptor

Antagonist

‘Inhibited’-ReceptorDENIED!

Non-competitive Inhibition

Drug Receptor Interactions

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

Low Affinity

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