Neurotransmitters 2 Flashcards
What is GABA? How is it synthesised? How does it act?
gamma-aminobutyric acid (GABA)
- is a inhibitory neurotransmitter that acts mostly via inhibitory interneurones
GABA is synthesised from glutamate via glutamic acid decarboxylase (GAD)
- GABA enters vesicles and gets released into synaptic cleft
- acts on GABA receptors on the neighbouring neurone and inhibits them
How is GABA regulated? Why must it be regulated?
deactivation
- reuptake into the GABAergic neurone by GABA transporters in the synaptic terminal
- breakdown by GABA transaminase
too much GABA
- excessive inhibition
too little GABA
- hyperexcitability
What type of receptor is GABAa? What is its effect? What other substances can bind to it? What is their effect?
GABAa
- ionotropic receptor (ligand gated ion channel)
= activation causes the opening of chloride channels. the influx of chloride results in hyperpolarisation and inhibition of neighbouring neurone
benzodiazepines and barbiturates (channel modulators) can bind
- facilitate the opening of the channels
= increased frequency of opening
What type of receptor is GABAb? What is its effect? What other substances can bind to it? What is their effect? What drugs can act on it?
GABAb (dimer)
- metabotropic receptor (GPCR)
- inhibits calcium entry, adenylyl cyclase activation, neurotransmitter release
- opens potassium channels causing hyperpolarisation
baclofen can act on it
- inhibits glutamate release
- has an antispastic effect (suppresses muscle spasms)
- treats addiction = alcoholism
What is noradrenaline? Where is it found and where does it project to? What is its functions?
is a monoamine
adrenergic neurones reside in the locus coerulus and project to the:
- cortex, amygdala (emotionality), hippocampus (memory), hypothalamus, cerebellum
functions:
- stimulates arousal
- increases heart rate
- associated with drug addiction and gambling (risk taking)
- low levels cause depression
- antihypertensive
What are noradrenaline’s receptors?
are all metabotropic receptors (GPCR)
- alpha (A1 and A2) and beta (B1, B2 and B3) adrenergic receptors
presynaptic
- are inhibitory autoreceptors = alpha-2 adrenergic receptors
- carry out negative feedback mechanisms/regulatory systems
post synaptic
- carries the message/signal
How can noradrenaline concentrations be regulated?
decrease NA
- reserpine = depletes NA stores by inhibiting NA vesicular uptake
- monoamine oxidase B (MAOb) = metabolises NA
increase (treats depression)
- amphetamine = enters vesicles by displacing NA into the cytoplasm causing increased NA leakage out of the neurone
- cocaine = blocks NA reuptake
What are the pathways for DA transmission in the brain?
nigrostriatal
- substanstia nigra to the striatum (basal ganglia)
- for movement regulation (voluntary/purposeful)
mesolimbic
- ventral tegmental area to the nucleus accumbens and amygdala
- for pleasure and reward
mesocorticol
- ventral tegmental area to the cortex (prefrontal cortex)
- for cognition, working memory and decision making
tubero-hypophyseal
- directly into the hypothalamus which is connected to the pituitary gland by the hypothalamic pituitary axis (capillary system)
- for inhibition of milk production by inhibition of prolactin release from the pituitary gland, metabolism, immune system
How is dopamine synthesised?
tyrosine is the initial precursor - tyrosine hydroxylase acts on it DOPA - DOPA decarboxylase acts on it dopamine - dopamine beta-hydroxylase acts on it noradrenaline - phenylethanolamine N-methyltransferase acts on it adrenaline
What are the classes of DA receptors? What does DA function and dysfunction result in?
D1 receptors - D1 (striatum, hypothalamus) and D5
D2 receptors - D2 (striatum, limbic, thalamus), D3 (limbic) and D4 (cortex and limbic)
function:
- movement, hormone release (prolactin), vomiting
dysfunction:
- addiction, schizophrenia, stereotypy
What is serotonin? Where is it found and released? What is it involved in/function?
serotonin
- excitatory neurotransmitter
cell bodies are found in the raphe nuclei and project to:
- cortex (heightened perception)
- hypothalamus (reduced appetite)
- amygdala (elevated mood)
- cerebellum, hippocampus, spinal cord
function:
- mood (anxiety/depression), sleep/wake, psychosis, vomiting, appetite, pain/migraine
How is serotonin synthesised?
tryptophan - tryptophan hydroxylase acts on it 5-hydroxytryptophan - DOPA decarboxylase (L-aromatic acid decarboxylase) acts on it 5-hydroxytryptamine (serotonin)
How is serotonin regulated? Why is it important to regulate serotonin concentration?
reuptake by 5-HT transporters
metabolism by monoamine oxidase
inhibition by autoreceptor 5-HT 1D
too much:
- heightened perception, stimulation, reduced appetite, elevated mood
too little:
- depression, pain
What are the serotonin receptors?
are all metabotropic except 5-HT3
5-HT1 inhibitory, location: limbic system – mood, migraine
5-HT2 (5-HT2a), excitatory, location: limbic system & cortex
5-HT3 excitatory, location: medulla – vomiting
5-HT4 presynaptic facilitation (ACh) – cognitive enhancement
5-HT6 and 5-HT7 – novel targets, cognition, sleep
