DRUG RECEPTOR INTERACTIONS Flashcards
What is the fastest type of receptor response?
Opening or closing of Ion channels upon binding with a ligand
Define ‘mean channel lifetime’
The duration of the a response following activation of a ion channel by receptor binding
How do secondary messengers alter intracellular functions?
They generate protein kinase activation and phosphorylation of membrane proteins
Give an example of a second messenger.
Adenyl cyclase
What cyclicAMP?
A nucleotide synthesised from ATP by adenyl cyclase
how is cyclicAMP inactivated?
It is converted into 5’AMP by phosphodiesterases
What components are required to generate a secondary messenger?
- Receptor protein: that faces outside of the cell
- G protein: transmembrane protein that faces inwards (toward the cytoplasm)
- Adenyl cyclase
- cAMP dependent protein kinase
What is the effect of cholera toxin?
It inhibits the secondary messenger system. It binds to G protein in intestinal mucosa and prevents hydrolysis of GDP to GTP and therefore inhibits activation of adenyl cyclase which is used to produce other secondary messengers such as cAMP
What is the function of G proteins?
Hydrolysis GTP to GDP, in doing so it opens calcium ion channels resulting in calcium influx and activates adenyl cyclase.
What form is most calcium in the body present in?
It is in skeleton in the form of hydroxyapatitem
How much calcium is in the blood?
2.5mmol/l
What percentage of calcium in the blood is free and what percentage is bound to protein?
50% is free in the blood and 50% is bound to proteins or complexed with anions.
What percent of calcium is found intracellularly?
1%
What is the intracellular calcium concentratio?
10-7m
Which hormones and regulators act via calcium channels?
- muscarininc agonists
- a1 agonists
- histamine
- serotonin
What intracellular effects take place when intracellular calcium is increased?
-Minor membrane phospholipids (phosphatidyl inositol) break down which increases the permeability of the membrane to calcium
-‘Flip Flop’ mechanisms: phosphatidylethanolamine is converted into phasphatidylcholine, this further increases membrane permeability to calcium
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What intracellular protein controls the intracellular effects of calcium?
Calmodulin- activates many different intracellular enzymes
How is calcium-calmodulin complex inactivated?
Trifluoperazine (antipsychotic)
Where do steroid hormones bind?
DNA binding sites
How are steroids hormones able to bind to DNA?
They are lipophilic which means they can easily diffuse through the cell membrane as well as the nuclear membrane and bind directly to DNA. They increase the production of RNA polymerase and therefore increase transcription
What is ‘half maximal binding’?
It is a measure of the affinity of a ligand to its receptor. It measures how much ligand is required to bind to 50% of its available receptors.
What is a partial agonist?
A ligand that has both agonist and antagonist effects, therefore the maximal response is lower than a pure agonist.
