Transmitter systems Flashcards
What does an agonist do?
Stimulates a receptor by mimicking an NT, thus increasing the effects of that NT.
What does an antagonist do?
Blocks a receptor, thus preventing an NT binding and diminishing its effects.
“The CNS is inherently changeable and non-static.” True or false?
True.
What do the dendrites do?
Receive inputs from other neurons.
What does the axon do?
Propagate the AP.
Which part of the neuron generates the AP?
The soma.
Why is it difficult to localise drug effects to the CNS?
Because the same receptors are found throughout the body in the PNS.
What is meant by a ‘disorder of the CNS’?
Disorders that arise from abnormal neuronal function in the brain and spinal cord. Often this is closely linked to mental function.
Why is it difficult to measure drugs for CNS disorders?
Results are subjective, e.g. pain is not the same for everyone.
NTs only have effects in the brain. True of false?
False: they are also found throughout the body.
Define an NT.
A chemical that allows signal transduction between neurons, thus conveying information.
NTs are always agonists. True or false?
True.
Why does changing NT activity to treat disease have adverse effects?
Because the same NTs have multiple functions and numerous receptors throughout the body.
NT action can be a) fast and b) slow. Which kinds of receptors are involved in each case?
a) Ligand-gated ion channels
b) Modulated receptors (GPCRs)
Where are NTs synthesised?
In nerve terminals.
What does a transporter do?
Removes excess NT from the synapse. This terminates its effects and recycles it (NTs are re-uptaken into the neuron).
List 3 methods for increasing the effects of an NT.
- Add precursor molecules to increase synthesis
- Block re-uptake by transporters
- Excite receptors
Give examples of drugs that block re-uptake by transporters.
Cocaine, MDMA, depression treatments like SSRIs
Give examples of 4 drugs that excite receptors in place of endogenous NTs. State the receptors they excite.
- Heroin, opioid receptors
- Nicotine, nicotinic cholinergic receptors
- LSD, 5HT2A
- Cannabis, cannabinoid receptors
What is epigenetic regulation?
Changes to gene expression. There are NO physical changes to DNA sequences.
Give an example of how gene expression can be regulated.
By histone winding or methylation. Increased histone winding or methylation means transcription factors cannot access the genes, thus transcription is down-regulated and less protein is produced.
NTs can affect gene transcription. True or false?
True.
Why do drugs affect everyone differently? Refer to genes.
Genes are the basis of individual differences. Drugs mimic NTs and can thus regulate gene transcription.
What causes the release of NTs?
Ca2+
Describe how NTs are released.
An AP causes voltage-gated ion channels to open.
Ca2+ floods into the cell.
This causes mobilisation of vesicles to undergo membrane fusion.
There are 4 types of Ca2+ channel. What are they?
N, P, R and T
Receptors can be a) intrinsic or b) extrinsic. What do these terms mean?
a) Strings of amino acids that link in and out of the membrane.
b) Sit on the membrane, are not embedded in it
If a drug targets a pre-synaptic receptor, what does it affect?
NT release.
If a drug targets a post-synaptic receptor, what does it affect?
Activity of the post-synaptic neuron.
When dosing a drug, threshold value must be overcome. True or false?
True.
Does a higher dose of a drug increase its effects?
Yes.
In terms of maximal response, what do a) full agonists, b) agonists and c) partial agonists achieve?
a) Always reaches maximal response
b) Reaches maximal response but a higher dose is required than with a full agonist
c) Never reaches maximal response REGARDLESS OF DOSE
What are the monoamine neurotransmitters?
Dopamine, noradrenaline and 5HT.
What is dopamine involved in? List 4 things.
- Reward, stimulates the nucleus accumbens in the VTA
- Motor function
- Psychosis
- Nausea and vomiting
What is dopamine made from?
Tyrosine (an amino acid)
Give the synthesis pathway for dopamine.
Tyrosine, L-DOPA, dopamine, DOPAC and HVA
What are DOPAC and HVA?
Inactive metabolites
How many types of dopamine receptor are there?
5.
What pathway is noradrenaline involved in?
The sympathetic adrenomedullary system (the fight or flight response).
Noradrenaline is involved in arousal and fear.
When the body reacts to a stressor, noradrenaline is released. List 4 physiological effects of noradrenaline release.
- Increased heart rate
- Increased blood pressure
- Increased blood flow to muscles
- Increased mobilisation of glucose stores
What happens if a person has too little noradrenaline?
They suffer from motor retardation (lethargy) and are sleepy.
What happens if someone has too much noradrenaline?
They are nervous, have racing thoughts and high blood pressure etc.
If injected peripherally, noradrenaline cannot enter the CNS. Why?
It cannot cross the blood-brain barrier.
What kind of receptor does 5HT act on?
Always modulated receptors, these are slow acting
There are only a small number of small 5HT circuits, thus 5HT has a small effect in the brain/body. True or false?
False: it is true that there are only a small number of small circuits, but serotonin controls numerous functions so its effects are always profound.
List 9 things that 5HT is involved in.
- Pain, e.g. migraine
- Mood
- Attention
- Sleep
- Depression
- Hallucination
- Fear
- Anorexia
- Anxiety
What is glutamate?
The main excitatory NT in the brain, is always depolarising (generates APs).
Glutamate pathways are always short. True or false?
False: they are v. long
Glutamate is involved in LTP or ‘long term potentiation’, meaning it creates a lasting response. True or false?
True.
List 5 things glutamate is involved in.
- Pain
- Memory
- Attention
- Cognition
- Epilepsy
Glutamate is the only NT that causes excitotoxicity. What happens in excitotoxicity?
Glutamate receptors are inappropriately activated, e.g. prolonged synaptic levels cause continued stimulation of the post-synaptic neuron.
This results in the death of the post-synaptic neuron.
This leads to pain, memory loss or even death.
When can excitotoxicity occur? Give an example.
After ischemia (restriction of blood flow to tissues).
Glutamate has 4 major receptors. What are they and what are they involved in?
- AMPA = Na+ transport
- Kainate = Na+ transport
- NMDA = Na+ and Ca2+ transport
- Metabotropic (these are GPCRs)
What is the role of ACh?
Main motor NT.
There are 2 types of ACh receptor. What are they?
- Nicotinic
2. Muscarinic
Nicotinic cholinergic receptors are ligand-gated ion channels with fast responses. True or false?
True.
Muscarinic cholinergic receptors are ligand-gated ion channels with fast responses. True or false?
False: they are GPCRs and have slow responses as they involve second messengers.
What is GABA?
The main inhibitory NT, is always hyperpolarising to prevent the generation of NTs
What chemical is GABA made of?
Gamma-aminobutyric acid.
GABA is synthesised from glutamate. True or false?
True.
GABA only has localised effects. True or false?
True.
There are 2 main receptors for GABA. What are they?
- GABA-A: ligand-gated ion channel, causes a Cl- influx
2. GABA-B: GPCR modulated receptor
Describe how alcohol affects GABA transmission in a) low and b) high doses.
a) Alcohol causes GABA disinhibition, i.e. it prevents GABA from acting so the subject is energetic and chatty.
b) Alcohol stimulates GABA, so the subject becomes lethargic and sleepy.
Give examples of peptide NTs.
Substance P and opioids.
Opioids have 4 main receptors. What are they?
Mu, delta, kappa and ORL-1.
What do endogenous opioids do?
Modulate the pain response.
What can a) low and b) high doses of opioids produce?
a) Depression, Parkinson’s and Alzheimer’s
b) Pain, epilepsy and positive schizophrenia
Why is it that some people do not gain pain relief from opiate drugs like codeine?
They do not have sufficient enzyme to metabolise codeine into morphine.
