1. PHC 221 Part(I) Dr. Huda Al Salem Lecture (5)

2. Factors that affect the efficacy 1- Mechanism of biological response 2- Concentration-Response Curves

3. 1- Mechanism of biological response

4. Studying the structure of receptors The 1 st human receptors were isolated in 1970s.. Problems were.. 1- Difficulty in isolation 2- Disruption of lipid membrane by detergents 3- Conformational change occurs 4- Very small quantities Thus, could not be studied by x-ray crystallography How did they solve this problem?

5. Studying the structure of receptors Plants (Algae) were the solution as they have receptors just like those of human being. Advantage: could be grown in large amounts So, receptors were isolated in amounts enough for x- ray crystallography. When the 3D structure was determined, it was possible to produce receptor molecules by Cloning Techniques

6. Homework (2) -What is cloning? -Discuss –in brief- three techniques used for cloning

7. General mode of operation Ligands that bind to receptors are either.. endogenous substances; 1-hormones 2-neurotransmitters Or exogenous substances(Xenobiotic): 1-drugs 2-bacteria 3-viruses

8. Hormones could be.. 1-Steroidal hormones (Oestrogen) 2-Peptide hormones 3-Prostaglandins 4-Simple amino compounds (L-Thyroxine)

9. Neurotransmitters could be.. 1- Acetylcholine 2-Noradrenaline

10. 3-Dopamine 4-Serotonine (5HT)

11. General mode of operation Endogenous ligands are secreted according to.. Stimulus (stress, pain, odour) Or change in concentration of a compound in blood stream ( glucose level) Some sections of the structure of the ligand are complementary in shape to sections of the receptor, Thus..acting as a magnet for the receptor, called…….. N.B. Binding must not be too strong to prevent switching on or off for long period of time … Why?

13. Superfamily Type classified according to endogenous ligand Subtype classified according to exogenous ligand Individual receptors RECEPTORS Superfamily Type I Superfamily Type II Cholinergic receptors for ACh Muscarinic cholinergic receptors mAChR m1AChRm2AChRm3AChRm4AChRm5AChR Superfamily Type III Superfamily Type IV

14. Superfamily Type I

15. General mode of operation

17. Superfamily type I - They are mb-embeeded proteins act as ion channels -Amino acids are (20-25 aa)..arranged in the form of  -helix It has 2  subunits, so require 2 ligand molecules to activate the receptor…..opening of ion channel Example nicotinic ACh receptors that contain 2  and  subunits