07 Neurotransmitters Flashcards
4 neurotransmitters from lecture
- Glu - aa
- NE - catecholamine
- Neurotensin - neuropeptide
- 2-AG - neuroactive lipid
Synthesis pathways of glutamate
- from glutamine with glutaminase, primarily in astrocytes
2. from alpha-ketoglutarate in Krebs cycle, NAPDH
storage of glutamate
- vGLUT transporter into vesicles
- uses energy
Release of glutamate
-Ca+ influx
Autoreceptor
- Presynaptic neuron can have receptors for NT that it releases
- negative feedback
EAAT
Excitatory amino acid transporter
- membrane transporter for ceullar uptake of NT
- uses Na+ gradient, so secondary cotransport
glutamine-glutamate shuttle
draw it out
- Glu release as NT
- Glu uptake via EAAT in glia
- Glu–>Gln (Glu synthase)
- Gln leaves glia, enters neuron via EAAT
- Gln–>Glu (Glutaminase)
- Glu enters vesicles via vGLUT
Glutamate excitotoxicity
Too much Glu causes too much Ca+ influx, damages neuron. Ruptured neuron releases more Glu.
NMDA receptors–what does it do, what does it require to activate?
Ca+ channel opened by Glu, requires:
- Glu
- Glycine
- membrane depolarization (to remove Mg+ plug)
mGluR
- metabotropic Glu receptors
- are GPCRs
2-AG brain distribution
- striatum (caudate nucleus, putamen, globus pallidus)
- cerebellum
- limbic cortex
- hippocampus
- amygdala
2-AG synthesis
- PLC cleaves PIP2 to DAG and IP3
2. DAG lipase (activated by Ca+) cleaves DAG to 2-AG
2-AG storage and release
- Not stored in vesicles
- made “on demand” and released simultaneously
- diffuses through membrane
- therefore, release is regulated by DAG Lipase
Inactivation of 2-AG
- via intracellular MGL (monoacylglycerol lipase)
- cleaves 2-AG into glycerol and arachidonic acid
CB1 receptor:
- agonists
- location
- action
- mechanism
- cannaboid receptor (2-AG, THC)
- presynaptic terminal
- inhibits voltage-gated Ca+ channels, (retrograde inhibition of NT release)
- GPCR