T5 Signal Transduction Flashcards
How long can an AP be in SM cells?
Seconds long
What are pharmodynamics?
What the drug does the to body
What are theraputics?
Medicinal use of drugs
What is pharmacology?
The general science of drugs`
What is Ek?
The equilibrium potential for potassium
What causes the unequal distribution of charge across a cell membrane?
The different electrochemical and concentration gradients for ions crossing the cell membrane
How does the dose response curve change in the presence of a non-competitive antagonist?
It will shift downwards
What does inositol triphosphate do as a second messenger?
Opens Ca2+ on endoplasmic reticulum
Where does primary active transport get energy from?
ATP
Give an example of primary active transport.
Na+/K+ ATPase
What provides the current across cell membranes?
The conductance of ion channels
How long do phase I, II, III take?
10 years
What type is a steroid hormone receptor?
Intracellular
How permeable is the membrane to large uncharged polar molecules?
To a small degree
What does thrombin activate when it binds to the g-protein coupled receptor?
Phospholipase C
What type is the insulin receptor?
Tyrosine kinase
What will blocking voltage gated Na+ channels do?
Blocks propagation of AP
What will a graph of receptors occupied vs drug concentration look like?
Rectangular hyperbolic
How long will it take an impulse to travel a unmyelinated neuron with a small diameter?
0.5-2.5 m/s
What is threshold for voltage gated Na+ channels?
-60 mV
How much more permeable to K+ is the membrane than Na+ at rest?
100 x
Where does secondary active transport get its energy from?
Movement of a molecule down its electrochemical gradient
What do heterotrimeic G proteins do when activated?
The A-subunit dissociates from the B-Y subunit
What happens to the activation gate at maximum depolarisation of voltage gated Na+ channels?
It closes
How many times do G-protein coupled receptors cross the cell membrane?
7 times
Name a receptor which is catalytic.
Tyrosine kinase
How many subunits do nicotinic receptors have?
5
How long does an AP in a nerve last?
5 ms
What activates Ca2+ dependant protein kinase?
Ca2+
How long will it take an impulse to travel a myelinated neuron with a large diameter?
60-100 m/s
What is a physiological antagonist?
A drug which acts to produce an opposing effect on another by activating a different receptor
What happens in phase III?
Randomised drug trials
What is toxiciology?
Action of posions
What will a graph of receptors occupied vs log of drug concentration look like?
Symmetrical sigmoid
How can we work out the affinity of the antagonist?
-log of (the concentration of antagonist that necessitates
you double the agonist concentration to produce the same response, i.e. dose ratio= 2)
Which channels close in repolarisation?
Voltage gated Na+ channels
What causes the absolute refractory period?
The closed inactivation gates of voltage gated Na+ channels
What type is a nicotinic receptor?
Ion channel
What is membrane potential when all Na+ and K+ channels are open?
+50 mV
How are tyrosine kinase receptors activated?
Autophosphorylation
What does phosphodiesterase inhibit?
cAMP
What does the G protein activate when it binds to a B-adrenergic receptor?
Stimulates cAMP production
When are G-proteins active?
When bound to GTP
How permeable is the membrane to small uncharged polar molecules?
Very permeable
What are pharmokinetics?
What the body does to the drug
What does vasopressin activate when it binds to the g-protein coupled receptor?
Phospholipase C
Where are GLUT1 receptors found?
Ubiquitous, in most cells incl. blood brain barrier
What is KD?
The drug concentration at which half the receptors are occupied
How permeable is the membrane to hydrophobic molecules?
Very permeable
What will the dose response curve of a partial agonist look like compared to a full agonist?
Lower and to the right
Where are GLUT4 receptors found?
Muscle, adipocytes. Insulin dependant.
How is NO produced from arginine?
Via NO synthase
What is a chemical antagonist?
A drug which inactivates the agonist
Where are GLUT2 receptors found?
Liver, pancreatic B cells
What does resting membrane potential usually equal?
Ek = -70mV
What is a chemical assay?
The first stage of drug development
What does glucagon inhibit when it binds to the g-protein coupled receptor?
cAMP production
How can we work out the potency of a drug?
Using EC50, the [drug] producing 50% of maximum response
What does the G protein activate when it binds to a muscarinic receptor?
Phospholipase C
What causes phosphorylation of serine residues?
Protein kinase A
How permeable is the membrane to charged polar molecules?
Impermeable
Where does insulin bind on the tyrosine kinase?
To the a-subunit
What is pharmacy?
Handling and formation of drugs
Which proteins associate with the ligand receptor?
Adaptor proteins
Which gates open when voltage gated Na+ channels depolarise to threshold?
The activation gate
What mediates insulins mitogenic pathways?
Ras
Where are sodium electrical and chemical forces flowing at rest?
Inwards
What kind of signalling do cytokines use?
Paracrine
What is the efficacy of a competitive antagonist?
0
How does the dose response curve change in the presence of a irreversible antagonist?
It will shift right and down
What is protein kinase C activated by?
DAG
What is a pharmokinetic antagonist?
It alters the body’s handling of the agonist
Where is the AP in motor neurons usually initiated?
At the axon hillock
Where are GLUT3 receptors found?
Neurons
How long will it take an impulse to travel a myelinated neuron with a small diameter?
2-15 m/s
What type is a B-adrenergic receptor?
G protein coupled
What type is a cannaboid receptor?
G protein coupled
What mediates the metabolic effects of insulin?
Akt
What is orthodromic propagation?
In normal physiological direction
What type is a muscarinic receptor?
G protein coupled
What activates guanylate cyclase?
NO
What is the dose ratio?
The ratio the of the concentration of the agonist that produces the same response in the presence of the antagonist and without the antagonist
Where is the tyrosine kinase domain of the tyrosine kinase receptor located?
Extracellularly
Are ligand gated channels inotropic or chronotropic?
Inotropic
How does the dose response curve change in the presence of a competitive antagonist?
It will shift to the right
