Concept of agonists and antagonists in receptor activation and inhibition and significance in regulation of signaling.

BY – RAHUL KUMARM.Sc. LIFE SCIENCE3RD SEMESTERCUG/2014/1073

Objective: Ligand & its types

Agonist & Antagonist

Properties & Types of Agonist

Properties & Types of Antagonist

Significance in regulation of signaling

Classification of ligands:

• Ligands are classified by effect upon binding to the receptor. LIGANDS

Agonist

Antagonist

Comparison between agonist & antagonist: Agonist

• Derived from Latin word – contender.

• Aids in the enhancement of an action.

Antagonist

• Derived from Latin & Greek words – competitor or opponent.

• Opposes the action of agonist and block the reception.

Properties of agonist:

Acute Signaling

Desensitization

Sequestration

Resensitization

Receptors can be activated either by endogenous or exogenous , leads to change in the biological response.

Types of agonist- a) Full agonist b) Partial agonist c) Inverse agonist

Full agonist – The ligands that increase the activity of the receptors & produce the maximal response . Ex.- Morphine ,mimics the action of endorphins at opioid receptors.

Partial agonist – These ligands partially increase the activity of the receptors but do not produce the maximal response like full agonist even when present in excess amount. Ex.- Buspirone , is an anxiolytic drugs , used to treat an anxiety disorder.

Inverse agonist – The ligands which decrease the activity of an active receptors to their inactive state. Ex.- Flumazenil drugs acts as a inverse agonist for the GABA receptor & produce anxiogenic effect.

Properties of Antagonist : Site selectivity. Structural conformation – mimics with the natural ligand.

Reduces the response.

Effect may be temporary or permanent.

Competitive

Types of antagonist-

Reversible

Irreversible

Non-competitive

Competitive antagonists – The antagonist competes with the agonist for the orthosteric sites for binding to the same receptor . - The effect of the antagonist can be overcome by increasing the concentration of the agonist.

Ex.- IL-1RA protein competes with IL-1 for binding to the cell surface interleukin-1 receptor.

Non-competitive antagonists : The antagonist binds at a different site other than orthosteric site on the receptor. - The effect of the antagonist cannot be overcome by increasing the concentration of agonist. Ex.- Binding of cyclothiazide with mGLUR1 receptor.

Irreversible antagonists: May or may not competes with the agonist for orthosteric sites for binding to the receptor. - Forms covalent bond to the site.

Ex.- Aspirin.

Significance of regulation in signaling:

REFERENCES - The cell (5th Edition) Cooper & Hausman Lehninger principle of biochemistry (5th Edition) Principles & Techniques of Biochemistry & Molecular biology (7th Edition) by Kleith Wilson & John Walker Handbook of cell signaling Vol.1 (2nd Edition)

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