Neurotransmitter Review Flashcards
Molecular structure of Ligand-gated ion channels
4 transmembrane regions of a subunit, 4-5 subunits combine to form a channel.
GPCR Structure
Single polypeptide with 7 TM domains
Neurotrophic factor reception
Usually dimerized receptors that are TKs.
Major excitatory NT
Glu, very ubiquitous and only a minute fraction is packaged into vesicles.
Two types of Glu receptors
Ligand Gated Na/Ca channels = AMPA, NMDA, Kainate
GPCR = mGluR 1-8 (Modulatory effects and autoreceptors)
How to astrocytes regulate glutamatergic transmission?
They buffer synaptic glutamate levels and protect nearby neurons from excitotoxicity. Astrocytes take up glutamate using GLT-1 (also transport K and Na).
Major inhibitory NT
GABA, 40-50% of neurons use.
Two major classes of GABA receptors
Ligand gated Cl channels = GABAa
GPCR= GABAb (modulatory effects and autoreceptors).
How is GABA synthesized?
It is made from glutamate via glutamic acid decarboxylase, and degraded by GABA transaminase.
How do sedative hypnotics (Benzos, barbiturates, alcohol) work?
By promoting the activity of GABAa receptors.
How do anticonvulsant drugs (like vigabatrin) work?
By promoting GABA synthesis or preventing its degradation/reuptake.
Major inhibitory NT in spinal cord?
Glycine
How to induce seizures?
Glycine receptor antagonists, like strychnine.
Class of glycine receptors
Strychnine-sensitive glycine receptor (ligand gated Cl- channel)
What else is glycine good for?
Co-agonist for NMDA receptor (not responsive to strychnine)
Catecholamine degradative enzymes
MAO and COMT
Catecholamine synthesis pathway
Tyrosine (TH) L-DOPA (AADC) Dopemine (DBH) NE (PNMT) E
Three major dopaminergic pathways in brain
1) Nigrostriatal (movement)
2) Mesocorticolimbic (VTA to NAcc) – motivation/addiction/emotion
3) Tuberoinfundibular (Arcuate nucleus to anterior pituitary) – prevents release of prolactin
Dopamine Receptors
All GPCR
D1, D5 – Gs
D2, D3, D4 –Gi, autoreceptors
Antipsychotic drug action
D2 antagonists.
Psychostimulant (meth, cocaine, ritalin)
Inhibit reuptake or stimulate release of DA.
Treatment of PD
L-DOPA or D2 agonists.
Noradrenergic projections
Locus ceruleus and other brainstem nuclei to cortex, cerebellum, and tectum.
Noradrenergic receptors
All are GPCR
B – GS
a1 – gq
a2– gi (autoreceptor)
Antidepressant drug effect on NE
Suppress reuptake
Synthesis of serotonin/melatonin
Tryptophan (tryptophan hydroxylase) 5HTP (AADC) 5HT (5HT N-acetylase) 5HT N-acetylase (5hydroxyindole o methyltransferase) melatonin
Where is melatonin utilized?
Pineal gland. Function unknown.
Serotonergic Projections start from…
Dorsal raphe nucleus (midbrain)
5HT receptors
5HT1 – Gi, autoreceptor
5HT2 – Gq
5HT3 – ligand gated
5HT4-7 – Gs
Functions of serotonin
Regulating stress responses and emotional behavior, regulating eating/weight control
How do antidepressants affect 5HT
Prevent reuptake
New antipsychotic drugs
D2 antagonists, but also block 5HT2a receptors.
Hallucinogens
5HT2a partial agonists
Antimigrane Drugs (triptans)
5HT1d agonists.
Acetylcholine synthesis
Choline + Acetyl CoA (Choline acetyltransferase) Acetylcholine (AChE) Choline + Acetate
Most important ACh Projection in brain
Hippocampus
Acetylcholine in striatum?
yes in interneurons
Acetylcholinergic projections
1) Basal forebrain nuclei (medial septal nucleus, diagonal band, nucleus basalis) project to hippocampus and are important for cognition.
2) Brainstem nuclei (dorsolateral tegmentum in pons) project widely and are important for sleep.
Why is smoking addictive?
Nicotine is a strong partial agonist at central nicotinic cholinergic receptors, which activate dopaminergic neurons in the VTA
Acetylcholine and PD
mAChR antagonists used to treat PD (work via striatal circuits), also D2 agonists.
AChE inhibitors treat?
Treat dementia (via hippocampal circuits)
Side effects of ACh antagonists
tachycardia, dry mouth, blurred vision
Botox
Blocks ACh release
Curare
Blocks NMJs.
Histamine Synthesis
From histidine (histidine decarboxylase) histamine
Where is histamine used?
Used solely by the tuberomammilary nucleus in hypothalamus.
Histamine receptors
All GPCR
H1 – most important in brain
H2 – inhibits stomach acid
H3 – autoreceptor
Function of histamine in CNS
Promotes sedation
Where does peptide synthesis occur?
Cell body, must be transported. Also enzymatically degraded (irreversible)
What type of receptors do peptide NTs use?
GPCRs only
Types of peptide NTs
Hypothalamic factors (CRF, TRF, GnRF)
Feeding and Gut peptides (NPY, cholesystokinin, VIP)
Tachykinins (substance p–nociception)
Orexin used where?
Lateral hypothalamus, but widespread projections
Orexin receptors
OX1, OX2 (GPCR)
Function of Orexin
Wakefulness
Narcolepsy
caused by death of orexigenic neurons
Three opioid peptides
Enkephalins (preproenkephalin)
Endorphins (POMC)
Dynorphin (preprodynorphin derived)
Mu delta kappa
Nucleoside NTs
ATP released with most NTs, converted to adenosine in synaptic space, many different receptors.
Adenosine function
Accumulates during wakefulness to promote sleep, sleep reduces adenosine levels
Caffeine
Adenosine receptor antagonist.
Endocannabinoids
Anandamide and 2-AG
Synthesis of endocannabinoids
Synthesized postsynaptically in response to Ca influx, then released into synapse to act on CB1 and CB2 receptors on presynapse.
NO as a NT
Synthesized postsynaptically by NO synthase which is activated by Ca, diffuses to presynapse where it activates cyclic GMP to modulate NT release
Main function of retrograde messengers
Modulate NT release.
