Amine Neurotransmitters Flashcards
Amine Neurotransmitters
Noradrenaline
Dopamine
5-hydroxytryptamine
Acetylcholine
Key roles of amine neurotransmitters
Roles in arousal, attention, sleep and survival
Speed of amine system modulation
Can modulate fast excitation or inhibition.
Via multiple receptors
Location of amine systems
Cell bodies restricted to a small number of brainstem nuclei
Gathered together in clusters, based on which NT they produce
Axons project widely and diffusely throughout the nervous system
Unlike glutamate and GABA, amine NTs lack…
Specialised synaptic contacts
Noradrenaline pathways in the CNS
Origin in the brainstem (locus coeruleus)
Diffuse innervation of forebrain, particularly the cerebral cortex
Also descending pathways
Where does noradrenaline bind
α1, α2, β1 and β receptors – GPCRs
Not at ligand gated ion channels
Role of noradrenaline in the brainstem
Blood pressure control
Baroreceptor reflex
Noradrenaline in descending pathways
Movement and pain
Noradrenaline in Ascending pathways
Arousal and mood
Cognitive processes, learning and memory, movement, attention
Noradrenaline synthesis
Tyrosine to L-DOPA by tyrosine hydroxylase
Decarboxylated to dopamine by dopamine dopadecarboxylase.
Taken into vesicles by vesicular monoamine transporter
Dopamine-b-hydroxylase converts it
Modulation of Noradrenaline synthesis
Hydroxylation of tyrosine to L-DOPA is rate limiting.
TH and DβOH synthesis can in increased on demand
Noradrenaline inactivation
Reuptake by NA transporters into presynaptic terminals
Degradation here by monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT)
Modulation of Noradrenaline inactivation
Uptake 1 is the most important transporter and can be blocked
Cocaine blocks uptake
Amphetamine makes reuptake transporters release NA
Dopamine pathways in the CNS have … origin
Midbrain
Dopamine pathways
Nigro-striatal
Mesolimbic/mesocortical
Tuber-infidibular
Mesolimbic/mesocortical pathways
VTA to cortex to hippocampus
(Ventral Tegmental Area)
Tuber-infidibular system
From hypothalamus to pituitary
Where does Dopamine act in the CNS
At D1-5 receptors
All GCPRs
Effects of dopamine
Control of movement (nigro-striatal)
Control of attention, emotion and reward
Control of endocrine function
Brainstem - vomiting
Synthesis of dopamine
Tyrosine to L-DOPA by tyrosine hydroxylase
Decarboxylated to dopamine by dopamine dopadecarboxylase.
Taken into vesicles by vesicular monoamine transporter
Inactivation of dopamine
Reuptake by DA transporters into presynaptic terminals
Degradation here by monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT)
Schizophrenia is caused by …
An overactivity on DA mesolimbic/cortical pathways
5HT pathways
Arise from raphe nuclei
Forebrain and from dorsal and median raphe
Caudal raphe to cerebellum
Pontine neurones to spinal cord
5HT receptors
5HT 1-7
Areas of 5HT action
Cortical/limbic system
Thalamus
Hypothalamus/limbic system
Gating of spinal transmission
5HT in the cortical/limbic system
Control of mood
Dysfunction in depression
5HT in the thalamus
Control of sleep
Activation = wakefulness/insomnia
Decreased activity = sleep and sedation
5HT in the hypothalamus/limbic system
Control of feeding
Increase = loss of appetite
Decrease = feeding/weight gain
5HT in spinal transmission
Control of sensory transmission
Gating of spinal transmission (pain)
Cortical inputs dampen sensory overload
5HT synthesis
Tryptophan is taken up and hydroxylated
Decarboxylation by AADC
Concentration into vesicles
Modulation of 5HT synthesis
Tryptophan hydroxylase is not saturated, therefore consuming more tryptophan can cause greater production.
Vesicular uptake can be blocked by reserpine
Reuptake of 5HT
Inactivation and reuptake by MAO
Uptake is specific for 5HT and can be blocked by SSRIs
Acetylcholine pathways in the CNS
Projection to cortex/limbic system from magnocellular neurons
Projection to hippocampus
Projections from brainstem to thalamus and other sites
Local interneurons in basal ganglia
Receptors for Ach
Both nicotinic (ionotropic) and muscarinic (GPCR)
Ach in the brainstem
Reticular activating system
Arousal, sleep and waking
Increased Ach = arousal
Ach in the basal forebrain nuclei
Cognition
Ach in the septo-hippocampal pathway
Learning and memory
Ach synthesis
Same as NMJ
Choline is taken up (active uptake)
Acetyl CoA is added by ChAT
Active transport into vesicles
Modulation of Ach synthesis
ChAT is not saturated, so dietary choline is rate limiting
Inactivation of Ach
Inactivation by acetylcholinesterase in the synaptic cleft, into free choline + acetic acid.
Active uptake of choline
