L4 Chemicals in the Brain Flashcards
How are amino acid, monoamine and acetylcholine neurotransmitters synthesised?
Locally in the presynaptic terminal.
How are amino acid, monoamine and acetylcholine neurotransmitters stored?
In synaptic vesicles.
How are amino acid, monoamine and acetylcholine neurotransmitters released?
In response to local increases in Ca2+.
How are neuropeptides synthesised, released and stored?
Synthesised in the cell soma and transported to the terminal.
How are neuropeptides released?
Released in response to global increases in Ca2+.
How are neuropeptides stored?
Stored in secretory granules (dense core vesicles).
Which neurotransmitters are fast?
Amino acids as they are docked in vesicles near the membrane.
Which neurotransmitters are slow?
Neuropeptides are they are larger and stored further away.
What frequency stimulations are required to release fast and slow neurotransmitters?
Fast NT- Low frequency
Slow NT- High frequency
Why do slow neurotransmitters require high frequency stimulation?
There needs to be a larger diffuse increase in Ca2+. High frequency is rapid and sustained.
What are the main excitatory neurotransmitters?
Depolarises.
Fast transmission.
Glutamate (AA, CNS).
What are the main inhibitory neurotransmitters?
Hyperpolarises.
Fast transmitters.
GABA (AA, brain).
Glycine (SC and BS, AA).
What is an example of a diffuse modulatory system?
Serotonergic system, a small set of neurones, that mostly arise from the brainstem, whose axons innervate far away.
(Also dopamine or acetylcholine)
What is the function of the serotonergic system?
Mood, sleep, pain, emotion, appetite.
What is a diffuse modulatory system?
Neurotransmitters that modulate rather than transmit information.
Where and how is glutamate synthesised?
Presynaptic terminal from Krebs glucose or glutamine (converted by glutaminase).
How is glutamate stored?
Loaded and stored in vesicles by vesicular glutamate transporters (VGLUTs).
How is glutamate reuptaken?
Excitatory amino acid transporters (EAATs_ in the plasma membrane and glia.
What go glia do to glutamate?
Convert glutamate to glutamine and transport it back to the nerve terminals where it it converted back to glutamate.
How many layers does the cortex have?
Six.
How is GABA synthesised?
From glutamate, catalysed by glutamic acid decarboxylase (GAD).
A higher proportion is made de novo than through recycling.
Main inhibitory enzymes can be synthesised from the excitatory.
How is GABA stored?
Loaded and stored in vesicles by a vesicular GABA transporter (GAT).
How is GABA cleared from the synapse?
Reuptake by glia and neurone transporters (co-transport with Na+), including those on non GABAnergic neurones.
What happens if you have too much glutamate or too little GABA?
Hyperexcitability leading to epilepsy and excitotoxicity.
What happens if you have too much GABA?
Sedation/coma.
What does cerebral ischaemia cause?
The metabolism that maintain the electrochemical gradient is abolished, Na/K gradient is reversed.
Transporters release glutamate leading to excitotoxic cell death.
How does excitotoxicity cause cell death?
Too much calcium from the excitement which activated enzymes that digest cells irreversibly.
Which neurotransmitters are local?
GABA, glycine and glutamate.
What is GHB?
Date rape drug.
GABA metabolite that can be converted to GABA, increases the amount causing unconsciousness/coma.
Which monoamine neurotransmitters are catecholamines?
Dopamine
Noradrenaline
Adrenaline (hormone)
Which monoamine neurotransmitters are indolamines?
Serotonin
How is dopamine synthesised?
Two stages.
From tyrosine to dopa and then dopamine.
What drug can be administered to increase dopamine levels and for which disease?
Levodopa (dopa) for treat Parkinson’s.
Converted to dopamine by dopa decarboxylase.
How are noradrenaline and adrenaline synthesised?
Only in the vesicles.
From dopamine to noradrenaline and then adrenaline.
How are the catecholamines stored?
Vesicular monoamine transporters (VMATs) load into vesicles via a proton gradient.
How are catecholamines released?
By Ca2+ dependant exocytosis.
How are catecholamines reuptaken?
Dopamine transporters (DATs) and noradrenaline transports (NETs) using an electrochemical gradient.
What happens after the reuptake of catecholamines?
Reloaded into vesicles or enzymatically degraded by monoamine oxidases (MAOs) or inactivated by catechol-o-methyl-transferases (COMT).
How does amphetamine (adderall) modulate the catecholamines?
Reverses the transporter causing the NT to be pumped out and blocks reuptake.
This lengthens the action.
How does cocaine and methylphenidate (Ritalin) modulate dopamine?
Blocks reuptake, extending action.
How does selegiline modulate dopamine?
MAO inhibitor, prevents breakdown so more is released in subsequent activations.
Use to treat early PD, depression and dementia.
How does entacapone modulate dopamine?
COMT inhibitor, increases amount of available NT.
PD treatment.
How is serotonin synthesised?
2 stages.
Tryptophan to 5-HD then serotonin.
How is serotonin stored?
Stored in vesicles.
How is serotonin reuptaken?
Serotonin transporters (SERTs). Destroyed by MAOs in the cytoplasm.
How does fluoxetine (Prozac) modulate serotonin?
Selective serotonin reuptake inhibitor (SSRI)
Treatment of depression and OCD.
How does fenfluramine modulate serotonin?
Stimulates release and blocks reuptake (appetite suppressant in obesity).
How does MDMA (ecstasy) modulate serotonin?
Amphetamine
Causes noradrenaline and serotonin transporters to run backwards, releasing NT into the synapse.
Therapeutic potential for PTSD.
How is acetylcholine synthesised?
Choline acetyltransferase converts choline and acetyl coA into acetylcholine which is packaged into vesicles by vesicular acetylecholine transporter (VAChT).
How is acetylcholine degraded?
In the synaptic cleft by acetylcholinesterase (AChE) and choline is transported back to form acetylcholine.
What are acetylcholinesterase inhibitors?
Block breakdown of ACh, prolonging its action in the cleft.
Neostigmine, used for myasthenia gravis (MG).
What are neuropeptides?
Slow transmission
Short peptide chains of 3-36 AAs.
Endorphins, substance P. neuropeptide Y, endogenous opioids and vasopressin (ADH).
How are neuropeptides synthesised?
Much faster than small molecule transmitters.
Secretory pathway.
Synthesised in the neurone nucleus, precursors and enzymes are transported down the axon to the terminal where the NP is produced.
How are neuropeptides degraded?
Proteases in the extracellular environment.
How can Nitric oxide by used in retrograde signalling?
NO is made in the postsynaptic by NO synthase, diffuses to the presynaptic where it acticvates guanylyl cyclase and cGMP.
Used in coord activités of multiple cells in a small region.
What gases can be a retrograde signal?
NO and CO.
What are endocannabinoids?
Small lipids which reduce GABA release at inhibitory terminals.
