BIOL 3020U Study Guide - Midterm Guide: Drug Metabolism, Endothelium, Endoplasmic Reticulum
Chapter 3, Section 3: Receptors
There are four types of receptors which drugs can act:
1. Ligand-gated ion channels (ionotropic receptors)
- Direct the flow of ions across membranes once activated by ligand
- Ex nicotinic acetylcholine receptor, regulate contraction on muscles and regulates firing
of neurons. Natural ligand is acetylcholine, Conducts .
Nicotinic Acetylcholine Receptor
- Made up of 5 protein subunits, anchored to the plasma membrane in a ring
- Each subunit contains: Binding domain at the N-terminus, hydrophobic amino acids that
interact with the plasma membrane
- Regions and domains are names M1-M4
- M2 forms the lining of the channel pore, has a kink that forms the channel gate and is
made up of hydrophobic amino acids like Valine and leucine
2. G-protein-coupled receptors (metabotropic)
- Consists of a single polypeptide chain, N-term binding domain, intracellular C-term, 7
transmembrane domains M1-M7, a G-protein coupling domain
- Bind extracellular ligands, the activated receptor then interacts with G-proteins (which
have 3 domains and )
- subunit binds GDP, once a conformational change in receptor which allows it to interact
with the subunit, it allows GDP to get replaced by GTP and dissociates the and
subunits. Then interact with its targets (ex enzyme or ion channel) and everything
becomes terminated after the target is activated or inhibited by the subunit converts
GTP back to GDP.
- Example muscarinic acetylcholine receptors are inhibitory (slows the heart rate) and
-adrenoceptors (agonist is adrenaline, epinephrine) are stimulatory (increases heart
contractions) to the enzyme adenylate cyclase (AC) which makes cAMP (bind and
activate protein kinase)
Protein Kinases regulate the function of many different cellular proteins
- Other enzymes
- Transporters
- Ion channels
- Contractile protein in smooth muscle
- Activates voltage-gates channels in heart cell (increasing contraction)
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Phospholipase C
- Produces two intracellular messengers, and DAG
- acts to increase free cytosolic by releasing from intracellular compartments. This can
initiate: contraction, secretion and enzyme activation
- DAG activates protein kinase C, which is turn controls many cellular functions by
phosphorylating a variety of proteins. Ion channels mostly calcium and potassium by
sometimes sodium channels.
3. Kinase-linked receptors
4. Nuclear receptors
Chapter 2, Section 4: Pharmacodynamics and toxicology testing
Receptor: a protein that is activates by an agonist (found naturally in the body) to produce a
physiological response and can interact with antagonist.
Affinity: tendency of a drug to bind to the receptor
- Agonist can have both affinity and efficacy. Antagonist can only have affinity.
To determine affinity, various conc of radio labeled drug are incubating with a homogenate
tissue that has the receptor of interest. Measure the amount of drug binding to receptor at each
drug concentration.
- is equal to the conc of the drug where 50% of the maximal binding occurs. The higher
the affinity the lower this number will be.
- represents the density of receptors (or binding sites).
- This is where all of the receptors are occupied by drug (saturation)
- , B is the amount of drug bound, is the conc of drug and is the affinity
- Certain rates that drugs bind with receptors
- Certain rates which drugs dissociate from receptors
- , when is low, affinity is high
Efficacy: tendency of a drug to activate the receptor
Determine effect of the drug:
- The effect is measured by its physiological response
- Illustrated by a concentration-response curve
- Allows to estimate the maximal response that the drug can produce (Emax)
- Dose needed to produce 50% maximal response is
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Document Summary
There are four types of receptors which drugs can act: Direct the flow of ions across membranes once activated by ligand. Ex nicotinic acetylcholine receptor, regulate contraction on muscles and regulates firing of neurons. Made up of 5 protein subunits, anchored to the plasma membrane in a ring. Each subunit contains: binding domain at the n-terminus, hydrophobic amino acids that interact with the plasma membrane. M2 forms the lining of the channel pore, has a kink that forms the channel gate and is made up of hydrophobic amino acids like valine and leucine: g-protein-coupled receptors (metabotropic) Consists of a single polypeptide chain, n-term binding domain, intracellular c-term, 7 transmembrane domains m1-m7, a g-protein coupling domain. Then interact with its targets (ex enzyme or ion channel) and everything becomes terminated after the target is activated or inhibited by the subunit converts. Example muscarinic acetylcholine receptors are inhibitory (slows the heart rate) and.
