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1- Mechanism of biological response
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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