neuro: neurotransmitter systems 3: monoamines Flashcards
what CNS control behaviour?
-autonomic nervous system
- hypothalamic-pituitary neurohormones
- diffuse monoamine system
what are monoamimes?
they are a group of neurotransmitters that consist of: serotonin, dopamine, adrenaline and noradrenaline.
what are the four main systems we talk about when discussing the diffuse monoamine system?
- noradrenergic locus coeruleus
-serotonergic raphe nuclei - dopaminergic substantia nigra and ventral tegmental area
- cholinergic basal forebrain and brain stem complexes
signalling in the nervous system can be fast or slow, describe the fast and slow signalling?
fast point to point signalling:
-neurotransmitters producing either inhibitory/excitatory potentials
-ligand gated ion channels
-glutamate, GABA Ach
Slow point to point signalling:
-neurotransmitters and neuromodulators
-G protein coupled receptors
-monoamines, peptides, Ach
difference between point to point and diffuse modulatory systems?
- point to point is faster, whereas diffuse modulatory system is slower and widespread.
Give some examples of metabotropic receptors and their consequent actions upon stimulation.
5HT1: inhibits adenylate cyclase
5HT2: stimulates phospholipase C
Dopamine D1: stimulates AC
Dopamine D2: inhibits AC
Noradrenaline β: stimulates AC
Noradrenaline α1: stimulates phospholipase C
Noradrenaline α2: inhibits AC
Describe the noradrenergic monoamine system
-consists of neuroadrenergic neurones that which project from the central core –> the locus ceoruleus (LC)
they project to several areas of the brain:
-the cortex
-the cerebellum
-the spinal cord
-the hypothalamus
etc
mention the effects of noradrenaline?
-Noradrenaline is very important for brain arousal; allows us to think fast and take action.
-it affects the cardiovascular system by increasing our heart rate and blood pressure.
- when gambling, we get a neuroadrenergic surge, which plays a role in addiction.
where does adrenaline come from?
-it is made in the synaptic terminals.
-tyrosine is the precursor that is the starting point for the production of adrenaline
Describe mechanism of how tyrosine is converted into adrenaline?
tyrosine —> DOPA catalysed by tyrosine hydroxylase
DOPA–> dopamine catalysed by DOPA decarboxylase
Dopamine–> noradrenaline catalsyed by dopamine beta- hydroxylase
Noradrenaline —> adrenaline catalysed by phenylethanolamine N-methyltransferase
how is NA regulated?
-NA is synthesised in the synaptic ending of noradrenergic neurones.
briefly describe the effects of noradrenaline and adrenaline on g couples protein receptors (recap from yr1)
- we have alpha1, alpha2 and beta receptors
alpha1 (Gq couples receptor) –> stimulate phospholipase C which then converts PIP into IP3 and DAG, this then increases calcium concentration to induce smooth muscle contraction (vasoconstriction)
alpha2 (Gi couple receptor) —> inhibits adenyl cyclase which inhibits production of cAMP and
how do we make sure that there is not a high amount of noradrenaline left in the synaptic cleft?
-Noradrenaline is reuptook into the neurone and then an enzyme called monoaminoxidase destroys (metabolises) the monamine (noradrenaline)
what is amphetamine?
-amphetamine enters the vesicles displacing NA into the cytoplasm, increasing NA leakage out of the neuron.
what are autoreceptors?
autoreceptors (for example alpha 2 receptors on the presynaptic neuron) regulate the release of noradrenaline.
provides a negative feedback loop. Noradrenaline stimulates the alpha 2 receptors, which then inhibit the release of noradrenaline.
what drugs cause an increase of Na?
-Resperine - depletes NA stores by inhibiting vesicular uptake of NA.
- Amphetamine- enters vesicles and displaces NA into the cytoplasm. Increases NA leakage out of the neuron.
- Cocaine: blocks NA re-uptake.
what is dopamine? What is it involved in and what are some conditions related to it?
Dopamine is released from dopaminergic neurones and they project from the central core. There are a few paths in which dopamine can project 2.
it is involved in:
- movement
reward
inhibition of prolactin release
memory consolidation
what are some paths dopamine can project 2 and explain them and what disease they may be associated with?
- substantia nigra- projects to the striatum, which is involved in control/initiation of voluntary movement. Associated with Parkinson’s disease
- VTA- mesolimbic (the system that regulates motivations and impulses)
Dopamine projection in midbrain, important in addiction and schizophrenia/psychosis
-AC- nucleus accumbens (reward,pleasure part of the brain)
-tuberohypphyseal pathway: prolactin secretion
If hyperstimulation of dopamine occurs in these mesolimbic dopaminergic neurones releasing a lot of adrenaline in the medulla and hypocampus, it’s associated with psychotic like episodes. For example, schizophrenia, hallucinations
-an increase in dopamine therefore the reward feeling will be greater, which can lead to addiction.
what are the two types of dopamine receptors?
- D1 and D2 receptors.
what are the similarities and differences between the D1’s and D2’s like receptors?
Similarities:
-they are both G protein coupled receptors
Differences:
- D1 like receptors are Gs coupled (stimulate cAMP) and start phosphorylating
- D2 like receptors are Gi coupled (inhibit cAMP)
How is dopamine regulated? (termination and increasing levels)
-reuptake of dopamine via dopamine transporters from the synaptic cleft.
-when dopamine is inside of the neuron, it is broken down by monoamine oxidase B.
- dopamine activates the D2 receptor present on the pre and post synaptic neurone, this allows the inhibition of further dopamine release.
- you can increase dopamine levels by inhibiting the re uptake dopamine transporters, therefore dopamine cannot get back inside the neuron and will accumulate in the synaptic cleft.
what is selegeline?
it is an antiparkisonian drug
It inhibits monoamine oxidase B, and increasing dopamine.
describe the serotonergic system?
- released by serotonergic neurones
-the cell bodies of the serotonergic neurones is found in the raphe nuclei (which is towards the back end of the brain)
-it acts on receptors called: serotonergic receptors (5-HT) 
where are 5-HT3 (serotonin receptors) found?
-they are found in amygdala which elevates mood
-found in hypothalamus, which when activated; reduced appetite.
how is serotonin made?
it is made from “tryptophan”, which is then converted into 5-hydroxytryptophan by tryptophan hydroxylase
5-hydroxytryptophan is then converted into serotonin (5-HT)
5-HT is then converted into 5-HIAA by aldehyde dehydrogenase.
how is serotonin regulated?
-Stimukate a 5-HT neurone which then releases serotonin into the synaptic cleft which find acts in 5-HT receptors.
- there are 14 types of 5-HT receptors.
-5-HT3 is the only 5-HT receptor where it’s a ligand gated ion channel.
They can act like autoreceptors
(Same as the previous mechanisms)
describe monoamine transporters ?
- 12 transmembrane domains
- both ends are intracellular
- pumps monoamines in the neurones
- examples are dopamine (DA), noradrenaline (NA) and 5-HT (serotonin) transporters.
acetyl choline is part of what system?
-the diffuse neurotransmitter system.
what is ach involved in?
- some cholinergic neurones cell bodies are found in the nucleus basalis and they project to the cortex
And many more pathways
-Ach is involved in learning and memory. We know this bc of conditions it’s related to such as Alzheimer’s and dementia. People with these conditions have less cholinergic neurones.
-pain
- addiction. ach has nicotinic and muscarinic receptors.
where does ach come from?
- comes from AcCoa and choline via an enzymic reaction you get Ach.
-gets put into vesicles, when stimulated it is released and acts on nicotinic/muscarinic receptors.
How is Ach degraded?
It is destroyed via an enzyme called acetylcholinesterase
If you want the Ach to increase, inhibit the acetylcholinesterase enzyme.
