Chemical mediators Flashcards
What is a bioassay?
An experimental assay in which the conc or potency of a substance is measured by the biological effect it produces.
What are 3 uses of bioassays?
Pharmacological activity of an undefined substance.
Investigate function of endogenous mediators.
Measure drug toxicity.
What was the study using acetylcholine as an agent in chemical transmission of nerve impulses? What did this study show?
In the donor heart:
The vagus nerve was stimulated, heart rate slowed and a fluid sample was removed.
In the recipient heart:
The fluid from the donor heart was added and the heart rate slowed.
The study discovered chemical transmission.
Define a mediator
A chemical, peptide or protein that conveys information from one cell to another.
What is the criteria for a substance being a mediator? (1)
Released from cells in a sufficient amount to produce a biological effect in a specific time period.
What is the criteria for a substance being a mediator? (2)
When an authentic sample of the mediator is applied, it reproduces an identical biological response.
What is the criteria for a substance being a mediator? (3)
Interference with the mediator (synthesis, release or action) will alter the biological response.
How does synthesis of small molecular mediators occur?
Regulated through specific enzymes
Describe the pathway of Tyrosine -> Adrenaline
Tyrosine + Tyrosine hydroxylase ->
Dopa +DOPA decarboxylase ->
Dopamine +Dopamine beta-hydroxylase -> Noradrenaline + Phenylethanolamine N-methyltransferase ->
Adrenaline
What is the rate limiting step in the conversion of Tyrosine to Adrenaline?
The 1st step (Tyrosine hydroxylase)
How does synthesis of peptide mediators occur?
Regulated by transcription
Describe the process of synthesis, sorting, processing and secreting a peptide mediator
Proteins are threaded through RER membrane and packaged into transport vesicles. They travel to the Golgi where they are packaged into secretory vesicles. Processing occurs in the transport and secretory vesicles. These are released from the cell by exocytosis (either regulated secretion or continuous secretion).
Describe regulated secretion
Increased intracellular Ca2+/ other intracellular signals are stored in significant amounts in secretory vesicles.
Typically neurotransmitters/neuropeptides
Describe continuous secretion
Occurs continuously with little material stored in the secretory vesicles.
Typically clotting factors and plasma proteins
How are pre-formed chemical mediators released?
Via exocytosis
What are some examples of pre-formed mediators?
Neurotransmitters
Hormones
Neuromodulators
Cytokines
Growth factors
What is the faster storage+release method of chemical mediators?
Pre-formed in vesicles
Regulated secretion
How are “on demand” mediators released?
Via diffusion or constitutive secretion
What are some examples of “on demand” mediators?
NO
Lipid mediators (prostanoids)
What is the common regulator of mediator secretion?
Ca2+ mediated exocytosis
What hypothesis predicted the existence of vesicles? Explain it
The quantal hypothesis
An axon on a muscle cell was stimulated and the postsynaptic membrane potential was recorded.
Established that neurotransmitters were released from presynaptic vesicles in discrete ‘quanta’ - results were from action of acetylcholine on the postsynaptic cell.
What is the calcium sensor protein used in regulated exocytosis called?
Synaptotagmin
What is Synaptotagmin required for?
Efficient membrane fusion
Why must termination of a neurotransmitter occur?
To accurately represent the action potential frequency
What are 2 ways a neurotransmitter action can be terminated?
Enzyme reuptake
Uptake of neurotransmitters back into neurons/supporting cells
Describe the uptake of neurotransmitters back into neurons/supporting cells
Transporters in the plasma membrane are specific to neurotransmitters
Vesicular transporters load transmitters into synaptic vesicles
How do drugs interfere with chemical communication?
Target ion channels, receptors, synthesis, storage, release or degradation of a chemical mediator
What drug interferes with neurotransmission ?
Drugs that target transporters to prevent the reuptake of neurotransmitters
Fluoxetine (prozac)
What drugs of abuse target neurotransmission? What is their mechanism?
Amphetamines
Increase noradrenaline by displacing it from its vesicles (sympathomimetic action).
What drug targets ion channels which regulate neurotransmission?
Lignocaine (strepsils), Sodium channel blocker
Gabapentin
