Concepts of agonist and antagonist receptors

cell signaling mechanism

1. Concept of agonists and antagonists in receptor activation and inhibition and significance in regulation of signaling. By – Rahul Kumar M.Sc. Life science 3 rd semester CUG/2014/1073

2. Objective: Ligand & its types Agonist & Antagonist Properties & Types of Agonist Properties & Types of Antagonist Significance in regulation of signaling

3. Classification of ligands : Ligands are classified by effect upon binding to the receptor. LIGANDS Agonist Antagonist

4. Comparison between agonist & antagonist : Agonist Derived from L atin 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.

5. Properties of agonist : Acute Signaling Desensitization Sequestration Resensitization

6. 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

7. 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.

8. 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.

9. Properties of Antagonist : Site selectivity. Structural conformation – mimics with the natural ligand. Reduces the response. Effect may be temporary or permanent.

10. Competitive Types of antagonist- Reversible Irreversible Non-competitive

11. 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.

12. 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.

13. Irreversible antagonists : M ay or may not competes with the agonist for orthosteric sites for binding to the receptor. - Forms covalent bond to the site. Ex.- Aspirin.

14. Significance of regulation in signaling :

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

16. THANK YOU