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Synaptic Transmission 3 - Anandamide


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What is Anandamide? Components?
-Arachidonic acid
linked by an amide bond
Where is Anandamide found?
-Throughout the brain
-Striatum, limbic cortex, hippocampus, cerebellum.
What is Anandamide's receptor?
The same one activated by THC tetrahydrocannabinol
What is THC?
The active ingredient in marijuana
How does Anandamide function?
It MODULATES many systems/NTs:
-Behavioral motivations
-BP, cerebral blood flow
How is Anandamide made?
On DEMAND - simultaneous with release; by a 2-enzyme cascade.
What is the precursor of anandamide?
NAPE - n-arachidonylphosphatidyl ethanolamine
What are the enzymes that make anandamide?
1. Transacylase - makes the lipid precursor.
2. Phospholipase D - takes phosphatidate off Anandamide.
What is the principal regulatory mechanism for Anandamide synthesis?
Regulation of intracellular calcium - it is required in high amounts for NAPE synthesis.
When is Calcium high enough for anandamide synthesis?
During neuronal activity
So what induces Anandamide synthesis?
Neuronal activity!
How is Anandamide released?
Probably via diffusion through the membrane, may have a carrier protein.
What is Anandamide inactivated by?
FAAH - fatty acid amide hydrolase
What are the products of FAAH?
-Arachidonic acid
What regulates FAAH? Where is it located?
Unregulated - intracellular.
What are the 2 mechanisms of Anandamide inactivation?
1. Enzymatic (FAAH)
2. Reuptake carrier
What is the reuptake carrier for anandamide?
A passive transporter that cannot move it up its concentration gradient
What reduces the intracellular Anandamide concentration so reuptake could occur?
What is the receptor for Anandamide? What kind of receptor is it?
CB1 - Cannabinoid receptor
G-protein coupled
Where is the CB1 receptor found?
Almost always presynaptic
What is the function of CB1?
Inhibits opening of voltage operated calcium channels - inhibits NT release
What is the action of Anandimide called?
Retrograde inhibition
Why is Anandamide a retrograde inhibitor?
B/c its synthesis/release is induced by Calcium/neuron activity, and its action is to prevent opening of voltage-gated Ca channels - hence inhibits NT release.
What are 3 conditions in which Anandamide activity is increased?
1. Stroke
2. Seizures
3. Brain trauma
What is a CB1 receptor blocker?
What is the affect of Rimonabant?
Appetite suppresant
What does inhibiting FAAH in mice do?
Acts as an anti-anxiety

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