Chemical Messengers Flashcards
Where are neurons that make ACh? (2)
Brainstem.
Striatum of basal ganglia.
Function of ACh from the striatum?
Control of voluntary motion
Function of ACh from the brainstem?
Baseline excitation to cortex.
REM sleep.
ACh is synthesized from:
What transporter move ACh into a vesicle?
What removes ACh from synapse?
Choline and acetate.
VAChT.
AChE
Muscarinic receptors of ACh
M1
M4
M5
M1: neuronal. Gq.
M4: presynaptic autoreceptor; striatum of basal ganglia. Gi.
M5: cerebrovasculature; basal ganglia. Gq.
Location of nAChRs in the body (3)
NMJ
ANS
CNS
How can nAChRs allow Ca++ in?
There are 5 subunits and 16 genes. They can change their properties to allow Ca++.
Inhibitory AAs
GABA
Glycine
Where is GABA found?
Most in superior CNS. Decreases as you move inferiorly (SC has least).
Major inhibitory AA in CNS.
3 critical roles of GABA
Consciousness
Motor control
Vision (retina)
What is GABA synthesized from?
What enzyme is important in its synthesis?
How does it get into vesicles?
How is it removed from synapse?
Glutamate
GAD (glutamate decarb)
VGAT
GAT1, GAT2
GAT1 vs GAT2
GAT1 is on presynaptic terminals and reuptakes GABA.
GAT2 is on glia/astrocytes nearby that turn it into glutamine and that re-enters the presynaptic terminal.
GABA A receptor:
Modulators:
Ionotropic.
Increases Cl- –> IPSP
Modulated by Benzos, EtOH.
How can GABA receptors be used as a target for anesthetics?
GABA A exists on many extra-synaptic places, and therefore it is targeted.
GABA B receptor:
How does its location on the presynaptic or postsynaptic terminal effect its function?
Metabotropic.
Gi/Go pathways (+ K+ channels, - Ca++ channels).
Presynaptic: regulate NT release.
Postsynaptic: inhibits post-synaptic cell.
Location of Glycine:
Function:
Produced from:
How is it removed from synapse?
Most in SC, and decreased as you move superiorly.
Mediates spinal inhibitions.
Glycine
GAT proteins, or recycled
What is the receptor for Glycine?
What does it lead to?
What can potentiate it?
Ionotropic.
Influx of Cl- –> IPSP at SC.
EtOH and anesthetics potentiate it.
Stychnine function
Blocks the glycine receptor and can lead to convulsions
What protein allows for uptake of ATP?
VNUT
P1 receptors and ligand:
Postsynaptic vs presynaptic functions:
Receptors for adenosine on post-synaptic terminals.
Postsynaptic functions: Induce sleep and inhibit general neuronal functions.
Presynaptic functions: inhibit NT release.
P2X receptors and ligand:
Type of receptor:
ATP.
Ionotropic.
P2Y receptors and ligand:
Type of receptor:
ATP, ADP, UTP, UDP.
Metabotropic (Gi/Gq coupled)
Functions of the P2 receptors (3)
Learning
Memory
Modification of locomotor pathways
Locations of where opiods act (3)
Basal ganglia
Hypothalamus
Brainstem
General functions of opiods
Modify pain sensation
Effect mood/personality
Precursor molecules for:
Endorphins:
Enkephalins:
Dynorphins:
Nociceptins:
Endorphins: PCOM
Enkephalins: pro-enkephalins
Dynorphins: pro-dynorphins
Nociceptins: orphanin
How are opiods removed from synapse?
Reuptake are enzymatic destruction
u (mu) receptor type and its effects
Metabotropic: increase in K+ efflux –> hyperpolarization
Analgesia Respi depression Euphoria Constipation Sedation
Kappa receptor type and effects
Metabotropic: decrease Ca++ influx
Analgesia
Dysphoria (depression)
Delta receptor type and effects
Metabotropic: decrease Ca++ influx
Analgesia
2 identified endogenous cannabinoids
Anandamine
2-AG
Where are the 3 big locations of cannabinoids in the body and what does it effect?
Where else is it located?
Basal ganglia: mood, motor control.
SC: modulation of pain.
Cortex: neuroprotection.
Hippocampus and hypothalamus
Synthesis of cannabinoids (2)
Derived from membrane lipids (arachidonic acid) and occurs in presynaptic terminal.
CB1 receptor is found where?
What does it do there? Via which receptor pathway?
Found on presynaptic terminal of EAA and GABA releasing synapses.
Inhibits EAA and GABA release via Gi.
CB2 receptor is associated with what?
What does it do?
What disease is it associated with?
Immune system (microglia, gut, etc).
Anti-inflammatory effects.
May help remove beta-amyloid plaques in patients with AD.
