PHC 221Part(I)

Dr. Huda Al Salem

Lecture (5)

Factors that affect the efficacy

1 -Mechanism of biological response

2 -Concentration-Response Curves

1 -Mechanism of biological response

Studying the structure of receptors

The 1st human receptors were isolated in 1970s..

Problems were..1 -Difficulty in isolation

2 -Disruption of lipid membrane by detergents3 -Conformational change occurs

4 -Very small quantitiesThus, could not be studied by x-ray crystallography

How did they solve this problem ?

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 amountsSo, 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

Homework (2)

-What is cloning ?-Discuss –in brief- three techniques

used for cloning

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

Hormones could be..

1-Steroidal hormones (Oestrogen)

2-Peptide hormones

3-Prostaglandins

4-Simple amino compounds (L-Thyroxine)

OH

HO

Oestrogen

I

I

HO

I

I

CH2CHCOOHO

NH2

L- Throxine

Neurotransmitters could be..

1 -Acetylcholine

2-Noradrenaline

3-Dopamine

4-Serotonine (5HT)

CH2CH2NH2HO

HO

Dopamine

HN

HOCH2CH2NH2

Serotonine (5-HT)

General mode of operationEndogenous 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?

Type classified according to endogenous ligandSubtype classified according to exogenous ligand

Individual receptors

RECEPTORSSuperfamily Type I

Superfamily Type IICholinergic receptors for ACh

Muscarinic cholinergic receptors mAChRm1AChR

m2AChR

m3AChR

m4AChR

m5AChR

Superfamily Type III

Superfamily Type IV

Superfamily Type I

General mode of operation

Superfamily type I-They are mb-embeeded proteins act as ion channels

-Amino acids are (20-25 aa)..arranged in the form of a-helix It has 2a subunits, so require 2 ligand molecules to activate the receptor…..opening of ion channelExample nicotinic ACh receptors that contain 2a, b, g and d subunits