Tuesday 10 September 2013

Do all synaptic vesicles contain ATP?

"Interestingly, all synaptic vesicles contain ATP, which is co-released with one or more “classical” neurotransmitters. This observation raises the possibility that ATP acts as a co-transmitter. It has been known since the 1920s that the extracellular application of ATP (or its breakdown products AMP and adenosine) to neurons can elicit electrical responses" [Purves et al, Neuroscience, 2nd Edition, 2001]. The statement "all synaptic vesicles contain ATP" may sound dubious, and a professor who studies P2X receptors said "not true", but page 131 of 5th Edition (2012) contains the same text. This does not sound like a typographical error.

Glutamate is the most common excitatory neurotransmitter in the CNS and, by definition, it is stored in presynaptic vesicles. This raises an obvious question. Suppose that ATP is stored in all vesicles. They why is ATP stored with glutamate? And why would it be stored in all vesicles?

ATP binds to P2X ionotropic and P2Y metabotropic receptors. Adenosine binds to P1 receptors. Four subtypes of P1 receptors have been cloned: A1, A2A, A2B, and A3. Receptors for ATP and adenosine are widely distributed in the nervous system and other tissues (Burnstock and Sawynok 2010).

Caffeine and theophylline block adenosine receptors, so you might guess that adenosine makes you sleepy.

The other two classes of purinergic receptors are GPCRs; adenosine is the agonist for adenosine receptors, e.g. A1 and A2A, and ATP is the agonist for the the P2Y receptors.

If it is true that all synaptic vesicles contain ATP, then there must be a reason.


Burnstock and Sawynok 2010, Adenosine Triphosphate and Adenosine Receptors in Pain, Pharmacology of Pain, IASP Press, Seattle, p303.

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