CAL 3 Flashcards
What is 5HT
5-HT (5-hydroxytryptamine, serotonin) is an indolealkylamine neurotransmitter with an uneven distribution in the CNS.
what are the hallucinogenic effects of LSD due to
The hallucinogenic effects of LSD (lysergic acid diethylamide) are due to a direct interaction with brain 5-HT systems
what molecules is 5HT made out of
- carbon
- oxygen
- hydrogen
- nitrogen
what 5 steps does the transmission of 5HT involve
- Synthesis
- Storage
- Release
- Activation of 5-HT receptors
- Inactivation of 5-HT
describe how the synthesis of 5HT happens
- trytopathan is actively taken up into the nerve terminal
- it uses a large amino acid carrier therefore is subjected to competitive inhibition by amino acids such as valine and leucine
- trytoptophan is converted to 5HTP by trytoptophan hydroxylase
- 5HTP is then converted to 5HT via DOPA decarboxylase (also known as L aromatic decarboxylase)
describe how the storage of 5HT happens
Presynaptic vesicles.
- 5-HT is stored in vesicles, together with specific proteins. - Vesicles are recycled, so that once the transmitter has been released they can be refilled with newly- synthesised transmitter (and also with re-captured transmitter) and the cycle of release is repeated.
describe how 5HT is put into vesicles
- a carrier molecule couples 5HT with sodium in an ATPase dependent process
- this is because it is going against the concentration gradient
how many families are there of 5HT post synaptic receptors
7
describe how 5HT is inactivated
- 5HT goes back to the vesicles and is stored in them
- MAO degrades 5HT and turns it back to 5HTP
- 5HTP is then oxidsed to 5-HIAA
Where are the cell bodies of 5-HT neurones located
The cell bodies of 5-HT neurones are primarily located in the raphe nuclei which are located in the pons and upper brainstem.
what are the two subgroups of 5HT neurone cell bodies
- Caudal raphe nuclei
2. Rostral raphe nuclei
why is it difficult to asign specific roles to the group of 5HT fibres
Because there is widespread overlap of the projection fields of many of the nuclei it is often difficult to ascribe specific roles to many of the groups of fibres.
name some other areas neuronal cell bodies containing 5HT can be found
Neuronal cell bodies containing 5-HT are also found at other sites including, e.g. the locus coeruleus, which primarily consists of noradrenaline containing cell bodies.
Where is the caudal raphe nuclei found
The caudal raphe nuclei are located in the lower brain stem.
where is the rostral raphe nuclei found
The rostral raphe nuclei are located in the upper brainstem and 5-HT fibres project to forebrain structures.
where do 5HT fibres primarily project to
The 5-HT fibres primarily project to parts of the medulla and to the dorsal horn of the spinal cord.
what pathway provides the most extensive monoaminergic system of the brain
5-HT pathways provide the most extensive monoaminergic system of the brain.
describe what 5HT neurones are like during the day
The neurones have a characteristic pacemaker activity which is high during waking arousal and low during sleep.
what happens if 5HT function is altered
There may be altered 5-HT function in affective disorders, aggressive states and schizophrenia.
What are the subtypes of each of the 7 5HT receptors linked by
similarities in terms of sequence homology, presence or absence of introns in the genes, and transduction systems they are associated with.
what type of receptors are the 5HT receptors
5HT3 - ligand gated
- all others are G protein coupled receptors
How many subtypes are there of the 5HT1 receptor family and name them
5
- 5HT1A
- 5HT1B
- 5HT1D
- 5HT1E
- 5HT1F
what are all the 5 subtypes from the 5HT1 receptor family negatively coupled to
All five subtypes are negatively coupled to adenylate cyclase by a Gi/o protein.
What does the drug sumatriptan do
The drug sumatriptan binds to the 5-HT1DB (also known as the 5-HT1B) receptor and also to the 5-HT1D receptor.
- it is an antimigraine drug
what do the Gi/O protein coupled to the 5HT1A receptor do
The Gi/o protein coupled to 5-HT1A receptors also directly activates some K+ channels to reduce neuronal excitability.
Where is 5HT1A found ( subtype from the 5HT1 family) and what do they do
High densites in limbic areas (regulation of mood and anxiety) and spinal cord (pain perception).
- Somatodendritic autoreceptors located on 5-HT neurones in the dorsal raphe nucleus inhibit 5-HT release.
- Post-synaptic receptors hyperpolarize neuronal membranes by direct activation of K+ conductances by Gi/o.
Where is 5HT1B found and what do they do ( subtype from the 5HT1 family)
High densities in the striatum, hippocampus, cerebellum and layer IV of the cortex.
There are inhibitory autoreceptors located on 5-HT neurones and inhibitory heteroreceptors located presynaptically on other neurones.
Where is 5HT1D found and what do they do ( subtype from the 5HT1 family)
- 2 subtypes - 5-HT1Dα and 5-HT1Dβ.
- High densities in the olfactory system, striatum, cerebellum and parts on the limbic system.
- 5-HT1Dβ also known as 5-HT1B receptors are located on cranial blood vessels and are thought to be the target of the anti-migraine drug sumatriptan.
where are 5HT1E and 5HT1F found ( subtype from the 5HT1 family)
- Both are found in high densities in the hippocampus and cortex.
- 5-HT1F receptors also found in other brain areas and in the uterus.
what are the 5HT2 subtypes coupled to and what do they do
- All three subtypes are coupled to inositol phosphate turnover to increase formation of diacylglycerol and inositol-1,4,5-triphosphate.
what is the classical subtype of 5-HT2 receptor
5-HT2A
The 5-HT2C receptor corresponds to the……
receptor previously known as 5-HT1C.
name the subtypes of the 5HT2 receptors
5-HT2A
5-HT2B
5-HT2C
where is 5HT2A found and what does it do (subtype of 5HT2 receptor)
- widespread distribution with densities in the frontal cortex
- role in anxiety, depression, and nociceptive transmission
- In the periphery, it mediates contraction of vascular, tracheal and bronchial smooth muscle, platelet aggregation and increase in capillary permeability.
- Possible target for prophylaxis of migraine.
Where is 5-HT2B found and what does it do (subtype of 5HT2 receptor)
- High levels in the cortex and some limbic structures and several peripheral tissues (gut, heart, kidney and lung).
- Mediates contractions of the rat fundic strip, a classical preparation for studying 5-HT, and some other GIT smooth muscle.
- Unknown role in the brain.
where is 5-HT2C found and what does it do (subtype of 5HT2 receptor)
- Widespread spinal and supra-spinal distribution.
- Potential roles include regulation of feeding, locomotion, hormone secretion, depression and anxiety.
- Also located on the endothelial cells of the choroid plexus where they probably influence the rate of formation of cerebrospinal fluid.
What receptor type is the 5HT3 receptor
Ligand gated, cation-selective ion channels which mediate membrane depolarization/neuronal excitation.
where is the 5HT3 receptor found
- Mediate inhibition of release of a number of CNS transmitters.
- High densities of post-synaptic receptors in the hippocampus, amygdala, area postrema, and some primary afferent terminals in the dorsal horn of the spinal cord.
- Peripheral location in the gastrointestinal tract.
What does the 5HT3 receptor do
roles in emesis and possibly anxiety, neuronal migration and differentiation
- mediates fast excitatory transmission
