[smart (OP)]

The biological mecanism of arachidonic acid (AA) synthesis is poorly characterized.

My hypothesis is that arachidonic acid signaling induces on-demand 2-AG/anandamide trafficking through PLC and PPAR activation:

https://en.wikipedia.org/wiki/Phospholipase_C#Activation   
https://en.wikipedia.org/wiki/Arachidonic_acid#Synthesis_and_cascade_in_humans
https://en.wikipedia.org/wiki/Peroxisome_proliferator-activated_receptor_gamma#Function

However, could intracellular docosahexaenoic acid (DHA) delivery promote AA supplementation?

Is AA and DHA neurotransmitters for retrograde-mediated cellular trafficking and synapse formation?

[smart (OP)]

However, could intracellular docosahexaenoic acid (DHA) delivery promote AA supplementation?

DHA supplementation decrease AA content of brain phospholipids...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2578826/

[Bored chemist]

It's not a neurotransmitter.

[smart (OP)]

It's not a neurotransmitter.

Do you got evidence?

[smart (OP)]

As a putative neuromodulator, AEA that is released into the synaptic cleft is expected to be rapidly inactivated. In general, two possibilities are known to remove a transmitter from the synaptic cleft to ensure
rapid signal inactivation either reuptake or enzymatic degradation. An enzyme that catalyzes hydrolysis of
AEA, forming arachidonic acid and ethanolamine, was detected in rat brain tissue (Deutsch and Chin,
1993) soon after the discovery of AEA and is variously known as ‘‘anandamide amidase,’’ ‘‘anandamide
hydrolase,’’ ‘‘anandamide amidohydrolase,’’ or ‘‘FAAH’’ (see >Section 2.3 for detailed discussion).
The existence of a membrane transporter that mediates the uptake of AEA has also been investigated
(see >Section 2.4 for detailed discussion). Thus, the ability of brain tissue to enzymatically synthesize and
metabolize AEA and also the existence of carrier‐mediated transport mechanisms essential for termination
of the signaling effects of AEA and of specific receptors for the AEA suggest the presence of AEA‐containing
(anandaergic) neurons. Therefore, AEA may represent a member of a new family of fatty‐acid‐derived
neuromodulators (Ameri, 1999).

http://biomedphys.sgu.ru/Files/LIB/Springer/Handbook%20of%20Neurochemistry%20and%20Molecular%20Neurobiology%20--%20neurotransmitters/14.pdf

[smart (OP)]

In recent years, experimental evidence has suggested that the endocannabinoid system is a major player
among the neurotransmitter systems involved in the regulation of different alcohol‐related phenomena
including tolerance, vulnerability, reinforcement, and consumption (for more details, see recent reviews)
(Hungund and Basavarajapepa, 2000a, b, 2004; Basavarajappa and Hungund, 2002, 2005; Hungund et al.,
2002; Basavarajappa, 2006).

Arachidonic-acid derived endocannabinoids are fatty acid neurotransmitters.
 

[exothermic]

Arachidonic-acid derived endocannabinoids are fatty acid neurotransmitters.

Arachidonic acid is an unsaturated fatty acid.

The presence of arachidonylethanolamide, N-arachidonoyl ethanolamine, 2-arachidonoyl glycerol, ect. doesn't make arachidonic acid a neurotransmitter.

[smart (OP)]

The presence of arachidonylethanolamide, N-arachidonoyl ethanolamine, 2-arachidonoyl glycerol, ect. doesn't make arachidonic acid a neurotransmitter.

There can be no endocannabinoid synthesis without sufficient levels of arachidonic acid.

[exothermic]

There can be no endocannabinoid synthesis without sufficient levels of arachidonic acid.

That's irrelevant to the fact that arachidonic acid is a unsaturated fatty acid.... not a neurotransmitter.

[exothermic]

It's not a neurotransmitter.

Do you got evidence?

Do you have any conclusive data indicating that free arachidonic acid is a neurotransmitter or a retrograde messenger?

[smart (OP)]

Do you have any conclusive data indicating that free arachidonic acid is a neurotransmitter or a retrograde messenger?

Retrograde signaling depends on arachidonic acid. Endocannabinoids (which are composed of AA), are neurotransmitters, so I guess fatty acid neurotransmission is heavily dependent on levels of AA in the brain.

[smart (OP)]

There can be no endocannabinoid neurotransmission without arachidonic acid.

[exothermic]

Retrograde signaling depends on arachidonic acid.

There can be no endocannabinoid neurotransmission without arachidonic acid.

You still haven't provided any evidence indicating that arachidonic acid is a neurotransmitter in and of itself.

[exothermic]

Do you have any conclusive data indicating that free arachidonic acid is a neurotransmitter or a retrograde messenger?

Retrograde signaling depends on arachidonic acid.

"In the case of arachidonic acid, even though this fatty acid is released and increases excitatory synaptic transmission when coupled with presynaptic stimulation, it requires relatively high concentrations (110), and in CA1 neurons, AA effects are blocked by DL-2-amino-phosphopentanoic acid (APV) (111, 112), consequently limiting arachidonic acid's potential as a retrograde messenger."

http://m.jlr.org/content/44/12/2221.long

[exothermic]

so I guess fatty acid neurotransmission is heavily dependent on levels of AA in the brain.

Well I won't argue that.

[Bored chemist]

It's not a neurotransmitter.

Do you got evidence?

(I presume you mean do I have evidence)
Yes, obviously. I don't make statements without being able to back them up.
"Arachidonic acid is one of the most abundant fatty acids in the brain"
from here
https://en.wikipedia.org/wiki/Arachidonic_acid#Brain

To be useful as a transmitter of messages, you have to be able to change the concentration significantly and quickly. But the background concentration is huge, so you would need to synthesise and or remove huge quantities of it to send a signal.

How come you hadn't worked that out for yourself?

[chris]

There can be no endocannabinoid synthesis without sufficient levels of arachidonic acid.

That's like calling carbon a neurotransmitter because there can be no serotonin, adrenaline, noradrenaline or dopamine without carbon.

Arachidonic acid is a ubiquitous unsaturated long-chain fatty acid (20 carbon atoms and 4 double bonds). It's cleaved off phospholipids in cell membranes by an enzyme called phospholipase A2, which is activated by various cellular processes. It's used as the precursor for a range of chemical syntheses in cells, including prostaglandins, prostacyclin and leukotrienes. As such, it sits in the inflammation pathway and can certainly be considered a messenger of sorts, but it's definitely not a classical neurotransmitter.

[smart (OP)]

Arachidonic acid is a ubiquitous unsaturated long-chain fatty acid (20 carbon atoms and 4 double bonds). It's cleaved off phospholipids in cell membranes by an enzyme called phospholipase A2, which is activated by various cellular processes. It's used as the precursor for a range of chemical syntheses in cells, including prostaglandins, prostacyclin and leukotrienes. As such, it sits in the inflammation pathway and can certainly be considered a messenger of sorts, but it's definitely not a classical neurotransmitter.

Chris, arachidonic acid signaling is essential to dopamine neurotransmission. https://www.ncbi.nlm.nih.gov/pubmed/1909771

Also, I believe the pleiotropic roles of arachidonic acid in regulating RNA-mediated gene expression may influence eicosanoids synthesis in vivo. https://www.ncbi.nlm.nih.gov/pubmed/23956046

Does RNA-mediated neurotransmission makes any sense?

[chiralSPO]

Chris, arachidonic acid signaling is essential to dopamine neurotransmission.

So is potassium. That doesn't mean that potassium is a neurotransmitter. Dopamine is the neurotransmitter. That AA (or potassium, or sodium, or chloride, or ATP, etc.) is necessary for proper neuron function has little to do whether it is a neurotransmitter or not.

[smart (OP)]

Eicosanoids are different types of neurotransmitters. Arachidonic acid largely influence dopamine neurotransmission by RNA-guided transcriptional mecanism.

https://www.ncbi.nlm.nih.gov/pubmed/23956046