T1 L4: Chemicals in the brain Flashcards
How do neuropeptides act as neurotransmitters and how are they released?
They are synthesised in the cell soma and transported to the terminal and then stored in secretory granules. They are much larger than normal neurotransmitters. They’re released in response to global increase in Ca2+
Are amino acids as neurotransmitter fact or slow?
Fast
Are neuropeptides as neurotransmitters fact or slow?
Slow
What is the main excitatory neurotransmitter?
Glutamate (Glu)
How does Glutamate excite neurones?
It slightly depolarises the postsynaptic cell’s membrane
What are the 2 main inhibitory neurotransmitter?
GABA (gamma-aminobutyric acid) and Glycine (Gly)
How do GABA and Glycine excite neurones?
They slightly hyperpolarise the postsynaptic cell’s membrane
Where is GABA used within the body?
In the brain
Where is Glutamate used within the body?
In the CNS
Where is Glycine used within the body?
In the spinal cord and the brain stem
What functions does the Serotonergic system have?
Mood, sleep, pain, emotion, and appetite
Where is Glutamate produced?
It’s synthesised in the presynaptic terminal
- from glucose via the krebs cycle
- from glutamine converted by glutaminase into glutamate
What do vesicular glutamate transporters (VGLUT’s) do?
They load and store glutamate in vesicles
Which cells convert Glu into glutamate?
Glial cells
Which transporters reuptake glutamate (Glu) and where are they?
Excitatory amino acid transporters (EAAT’s) found in the plasma membrane of presynaptic cell and surrounding glia
What is GABA synthesised from?
Glutamate (Glu)
What catalyses the synthesis of GABA?
Glutamic acid dehydrogenase (GAD)
Which transporter loads and stores GABA?
Vesicular GABA transporter (GAT). Gly uses this transporter too
How is GABA cleared from a synapse?
Reuptake by transporters on glia and neurones
How much of GABA is recycled?
Not a lot. Most of it is made de novo to refill vesicles
What are the effects of too much Glu/ too little GABA?
Hyper-excitability (epilepsy) and excitotoxicity
What are the effects of too much GABA?
Sedation/ coma
What is cerebral ischaemia and what are the consequences?
It’s the metabolic events that retain the electrochemical gradient are abolished leading to reversal of the Na+/K+ gradient. It causes transporters to release glutamate by reverse operation causing excitotoxic cell death (too much Ca2+ release activates digestive enzymes that break down the cell)
What is GHB (gamma-hydroxybutyrate) and how does it work?
It the date rape drug. It’s a metabolite that can be converted back into GABA to increase the levels of GABA which will lead to unconsciousness and coma
Give some examples of Cetecholamines
Dopamine, Adrenaline, and Noradrenaline
Give examples of Indolamines
Serotonin
Describe the steps to synthesising dopamine
Tyrosine - dopa - dopamine
Does dopamine cross the blood-brain barrier?
No
What is the drug Levodopa used for?
Treating Parkinson’s disease
Describe the steps of synthesising adrenaline
Dopamine - Noradrenaline - Adrenaline
Which is the only neurotransmitter synthesised within vesicles?
Noadrenaline
What is Levodope (L-dopa) and how is it used?
It a precursor of dopamine and is used to treat Parkinsons disease. Dopa decarboxylase converts it into dopamine
How are catecholamines released?
By Ca2+ dependent exocytosis
How is the catecholamine signal terminated?
They are taken up into the axon terminal by transporters powered by electrochemical gradient (Dopamine transporters (DAT’s), and Norepinephrine transporters (NET’s))
Which enzymes degrade Catecholamines?
Monoamine oxidases (MOA’s)
Which molecules deactivate Catecholamines?
Catechol-O-methyl-transferases (COMT)
What effect does the drug Amphetamine have on Catecholamines?
It increases the release and decreases the reuptake of catecholamines like Dopamine and Norepinephrine
What effect does the drug Cocaine have on Catecholamines?
It increases the release of norepinephrine and of dopamine and inhibits their neuronal reuptake. This leaves more of them in the synaptic cleft and which extends their action on the postsynaptic neuron
What effect does the drug Methylphenidate (Ritalin) have on Catecholamines?
Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function
What effect does the drug Selegiline have on Catecholamines?
It’s an MOA inhibitor found in dopaminergic nerve terminals which prevents the breakdown of dopamine
It’s used as treatment for depression and dementia
What effect does the drug Entacapone have on Catecholamines?
It’s a COMT inhibitor that increases the amount of neurotransmitter
Describe the process of serotonin synthesis
Tryptophan - 5-HTP - 5-HT (serotonin)
Which precursor of serotonin is found in chocolate?
Tryptophan
How is the signal for serotonin terminated?
By reuptake by serotonin transports (SERT’s) on the presynaptic membrane or it’s destroyed by MAO’s in the cytoplasm
What effect does the drug Fluoxetine (Prozac) have on serotonin?
It’s an SSRI that blocks the reuptake of serotonin. It’s used as treatment for for depression and OCD
What effect does the drug Fenfluramine have of serotonin?
It stimulates the release of serotonin and inhibits it’s reuptake. It has also been used to supress appetite in obesity
What effect does MNDA (methylenedioxymethamphetamine) (ecstasy) have on serotonin?
It causes norepinephrine and serotonin transporters to run backwards so that they release neurotransmitter into the synapse. It has been assessed for therapeutic potential in PTSD
What does Choline acetyltransferase do?
It converts choline and acetyl CoA into acetylcholine
Which transporters package acetylcholine into vesicles?
Vesicular acetylcholine transporters (VAChT)
Which molecule rapidly degrades acetylcholine in the synapse?
Acetylcholinesterase (AChE). The choline is transported back into the presynaptic terminal and converted to acetylcholine again
What is the drug Neostigmine used to treat?
Myasthenia gravis. It’s a type of acetylcholinesterase inhibitor
What is Myasthenia gravis?
A rare long-term condition that causes muscle weakness. It most commonly affects the muscles that control the eyes and eyelids, facial expressions, chewing, swallowing and speaking
What triggers the degradation of neuropeptides?
Ca2+
How long do neuropeptides last?
The signal can be maintained for longer but they are released slowly
What role does nitric oxide have in the guanylyl cyclase pathway?
NO activates guanylyl cyclase which makes the second messenger cGMP
What do endocannabinoids do?
They are small lipids which mostly cause reduced GABA release at certain inhibitory terminals. They are believed to be related to addiction
What is the active component of cannabis?
A cannabinoid
