Neurotransmitter Systems Flashcards
Acetylcholine (Cholinergic) :
- Synthesis:
- Moved into clear vesicles via ?
- Removed from synaptic trough via ? bound to post-synaptic cell membrane
- Choline and Acetate
- Vesicular Ach Transporter protein (VAchT)
- Acetylcholinesterase
Acetylcholine (Cholinergic):
• Receptor Location
- M1 (neuronal): ↑ ? –>↑ ?
- ↑ IP3/DAG (Gq) –> ↑ Ca++
Acetylcholine (Cholinergic):
• Receptor Location
- M2 (cardiac): ↓ ? –> ↑ ? efflux
- ↓ cAMP (Gi) –> ↑ K+ efflux
Acetylcholine (Cholinergic):
• Receptor Location
- M3 (smooth m. of bronchi, vasculature; endothelial cells of vasculature
(NO): ↑ IP3/DAG (Gq) –> ↑ Ca++
- ↑ IP3/DAG (Gq) –> ↑ Ca++
Acetylcholine (Cholinergic):
• Receptor Location
- M4 (presynaptic autoreceptor; striatum of basal ganglia): ↓ ?
↓ cAMP (Gi)
Acetylcholine (Cholinergic):
• Receptor Location
- M5 (cerebrovasculature; dopaminergic neurons of basal ganglia): ↑ ?
↑ IP3/DAG
Acetylcholine (Cholinergic): • Nicotinic Receptors • Located at: - - Synapse between ? and ?cells in autonomic ganglia
• Located at:
- NMJ
- Synapse between pre- and post-ganglionic cells in autonomic gangli
2 major inhibitory amino acids
- GABA
- Glycine
Which area has the least GABA of all?
Spinal Cord
Roles of GABA
Multiple Roles but critical in:
- Consciousness
- Motor Control
- Vision (retina)
GABA
• Synthesis
- From ?
- Important Enzyme:
- Transported into vesicles by ?
- Removed from synapse via ?
- 2 Forms:
1. GAT1 - on the ?
2. GAT2 - on ? cells surrounding the synapse
• Synthesis
- From GLUTAMATE
- Important Enzyme: GLUTAMATE DECARBOXYLASE (GAD)
- Transported into vesicles by Vesicular GABA Transporter protein (VGAT)
- Removed from synapse via GAT (GABA Transporter)
- 2 Forms:
1. GAT1 - on the presynaptic terminal
2. GAT2 - on glial cells surrounding the synapse
If GAT1 (on the presynaptic terminal) takes the GABA up, the GABA is repackaged into ? as is.
vesicles
If GAT2 (on the astrocytes) takes the GABA up, the GABA is converted to ? and released to the ?, where it will be taken up by the ? and recycled into ?.
- Glutamine
- ECF
- Presynaptic terminal
- GABA
- Ionotropic (Cl conductance)
- Activation produces ipsp in adult neurons.
• Multiple binding sites modulate: - Benzodiazepine site - Ethanol - Certain steroids - These all potentiate.
GABA(A) Receptors
- Metabotropic
- Gi/Go protein coupled.
- Activate a K+ channel (GIRK)
- Close down (inhibit) a Ca++ channel
• Located pre- and post-synaptically
- Presynaptic: regulate NT release
- Postsynaptic: inhibition of post-synaptic cell
GABA(B) Receptors
Glycine: • Found in: - ? - ? - Much less in ?
• Found in:
- Spinal Cord (major)
- Brainstem (medulla)
- Much less in higher areas of CNS
Glycine:
- Function ?
Function
- Mediates many spinal inhibitions
Glycine:
- Production ?
Production:
- Unmodified amino acid
Glycine:
- Removal from synapse:
?
Removal from synapse:
- GAT proteins (same as GABA)
- Recycling
Glycine Receptor
- Ionotropic (Chloride)
- Influx of ? leads to ipsp
- ? and ? bind to it and potentiate
- ? binds to it and blocks it
- Influx of CHLORIDE leads to ipsp
- ETHANOL and GENERAL ANESTHETICS bind to it and potentiate
- STYCHNINE binds to it and blocks it
2 Major classes of purines?
P1 and P2
P1 (A receptors)
- ligand = ?
- Post-synaptic locations ?
- Pre-synaptic locations ?
- ligand = adenosine
- Post-synaptic locations
- Sleep induction
- General inhibition of neural function
• Pre-synaptic locations
- Inhibition of neurotransmitter release
P2 receptor = ?
- Ionotropic
- Ligand: ATP
- Many subtypes
P2X
P2 receptor = ?
- Metabotropic
- Ligand: ATP, ADP, UTP, UDP
- Gs/Gq coupled
P2Y
Functions of purines?
- Learning & memory (co-release with EAA)
* Modification of locomotor pathways
• These neurotransmitters are peptides made in the soma and transported
down the axon via fast axonal transport.
• Includes several transmitters:
- ?
Peptide Transmitters
Include:
- The opioids
- The tachykinins, including Substance P.
- Cholecystokinin
- Somatostatin
- others
• The opioids are a family of peptides that include:
?
- The endorphins (endogenous morphines – we knew about morphine first).
- The enkephalins
- The dynorphins
- Nociceptin
Functions of the Opioids?
- Modification of nociceptive inputs (Cutaneous senses).
* Mood/Affect
4 Precursor molecules of opioids?
• Proopiomelanocortinin (PCOM)
- Β-Endorphins
• Pro-encephalin
- Tyr-gly-gly-phe-X
- Met-enkephalin (X = methionine)
- Leu-enkephalin (X = leucine)
• Pro-dynorphin
- 3 molecules of Leu-enkephalin
- Dynorphin
• Orphanin FQ –> nociceptin
Synthesis of the opioids?
Standard protein synthesis in the cell body
Removal from trough/cleft of the opioids?
• Probable reuptake
• Enzymatic destruction
- Enkephalinase
- Aminopeptidiase
Opioid receptor
- u- Receptor (mu) = ?
Metobotropic receptor
***Opioid activation causes (u-receptor)?
- Analgesia
- Respiratory depression
- Euphoria
- Constipation
- Sedation
Opioid Receptor:
Kappa (K) receptor =?
Serpentine
Opioid (kappa) receptor produces:
- ?
- Analgesia **
- Dysphoria **
- Diuresis
- Miosis
Opioid Receptor
- Delta receptor = ?
Serpentine
Opioid (delta) receptor produces ?
Produces analgesia** when activated.
Opioid Receptor:
• All opioid receptors are ? (serpentine) and activate second messenger systems with ligand binding.
- All connect to ? proteins
- Mu receptor: leads to an increase in ? efflux
and hyperpolarization.
- Delta- and Kappa-receptors:
~Decrease ? influx.
• All opioid receptors are METABOTROPIC (serpentine) and activate second messenger systems with ligand binding.
- All connect to Gi/Go proteins
- Mu receptor: leads to an increase in POTASSIUM efflux
and hyperpolarization.
- Delta- and Kappa-receptors:
~Decrease CALCIUM influx.
Endocannabinoids:
• Broadly distributed in the CNS
• Basal ganglia functions:
- ?
• Spinal cord
- ?
• Cortex
- ?
• Hippocampus
- ?
• Hypothalamus
- ?
• Basal ganglia
- Mood
- Motor performance
• Spinal cord
- Modulation of nociception
• Cortex
- Neuroprotection
• Hippocampus
- Memory formation
• Hypothalamus
- Control of body
energy/hunger
Endocannabinoids synthesis:
- Derived from ?
- Occurs in ?
- Membrane lipids (arachidonic acid)
- presynaptic terminal
Endocannabinoid:
• The CB1 receptor:
- Found on pre-synaptic terminals of ? and ? releasing synapses
- ? EAA and GABA release.
- Via a ? coupled protein
- ? and ? are equally effective.
- Found on pre-synaptic terminals of EAA and GABA releasing synapses
- REDUCES EAA and GABA release.
- Via a Gi coupled protein
- ANANDAMIDE and 2-AG are equally effective.
Endocannabinoid:
CB2 receptor
• Associated with ?
- Location: ?
- Action: ?
- Special note: in the brain, activation of the CB2 receptor increases ?
CB2 receptor
• Associated with IMMUNE SYSTEM
• Location:
- Microglia in brain
- Gut
- Immune system in general
- Action: ANTI-INFLAMMATORY
- Special note: in the brain, activation of the CB2 receptor increases β-AMYLOID REMOVAL.
