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TAAR1–Dopamine neuron pharmacodynamics diagram

[edit]

Voting period is over. Please don't add any new votes. Voting period ends on 7 Mar 2014 at 16:32:34 (UTC)

Original – In this diagram, amphetamine enters the presynaptic neuron across the neuronal membrane or through the dopamine transporter (DAT).[1] Once inside, it binds to trace amine-associated receptor 1 (TAAR1) or enters the synaptic vesicles through vesicular monoamine transporter 2 (VMAT2).[1][2] When amphetamine or a trace amine (e.g., phenethylamine) binds to TAAR1, it reduces postsynaptic dopamine receptor firing rate and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT phosphorylation.[1] Phosphorylated DAT then either operates in reverse or withdraws into the presynaptic neuron and ceases transport.[1] When amphetamine or a trace amine enters the synaptic vesicles through VMAT2, dopamine is released into the cytosol (yellow-orange area).[2][3]
Reason
It's a helpful visual aid for explaining a very technical concept – the pharmacodynamics or "mechanism of action" of TAAR1 agonists in dopamine neurons – where there are several paths associated with each compound as well as the signal transduction pathway from TAAR1. The diagram is an svg image with applicability to at least a dozen articles.
Articles in which this image appears
Currently: Amphetamine, Adderall, Dextroamphetamine, Phenethylamine, TAAR1, and Autoreceptor – (the first 5 are transcluded via {{amphetamine pharmacodynamics}} - this template displays the intended image size).
FP category for this image
Wikipedia:Featured pictures/Diagrams, drawings, and maps/Diagrams
Creator
Seppi333
  • Support as nominator --Seppi333 (Insert 2¢ | Maintained) 16:32, 25 February 2014 (UTC)[reply]
  • Oppose for now I'm sorry, I love to see these diagrams, but I'm having a hard time following. And coincidentally, I've published papers on dopamine D2 receptors, and had to make diagrams (though simpler). As for specific suggestions: if your interest is amphetamine, then why have it come from both the bottom left and bottom right? Why not one area with 2 different pathways it can take? Does the black arrow pointing down mean N-phenylalanine reduces the charge, or does it mean it's entering from outside of the synapse or from the axon? It's even hard to tell from a layman's perspective what part of the neuron you've zoomed in on. I think it needs re-imagining for clarity. This is all in the visualization, and not content. You've provided refs (thanks!) so I'll trust you that you've selected the pertinent components to show. Mattximus (talk) 21:42, 25 February 2014 (UTC)[reply]
I wouldn't mind reworking the image if you can give me some more pointers for improving clarity; that was actually the main reason I nominated this. ;) The model I was originally working with was from the Miller paper below - this figure.
The black arrow was meant to show it's entering from that direction (the axon). The bottom left/right was mostly just a result of the remaining space I had when designing it. If you can give me a rough sketch or specific points on how to improve the clarity, I'd be happy to redesign it. Seppi333 (Insert 2¢ | Maintained) 22:00, 25 February 2014 (UTC)[reply]
Edit/add: for reference, the location is the presynaptic neuron cutout from this diagram - {{Synapse map}}. I used that design since I linked to that page in several of the articles. Seppi333 (Insert 2¢ | Maintained) 22:03, 25 February 2014 (UTC)[reply]
If I have some time I would love to go over it. The Miller diagram, although not the prettiest picture, is pretty easy to follow and actually quite good. To start, would it be hard to give the axon a little lead room so we can see clearly it's an axon terminal? Maybe get rid of the black line and leave it open like in the article you sent? Mellow out the harsh yellow (I like just white but I can see value in distinguishing intra vs extra cellular space). If you do this you don't need to write "presynaptic neuron" because that doesn't really make sense (the whole thing really is the presynaptic neuron, not just the top) and cleans up the diagram a bit. You also should clarify the legend, it seems like the down arrow means reduces charge, not "coming from axon" as you have it. Does that make sense? I'll add more when time permitsMattximus (talk) 02:30, 26 February 2014 (UTC)[reply]
@Mattximus: I tried to address your comments in my recent revisions. The image insertion template which I linked above clarifies the L-phenylalanine -> Phenethylamine step by annotating "Via AADC". Should I just incorporate that text into this image and then make a duplicate image without that text for this template? My other question is the color - the yellow-orange area looks (very) bad if I fade it, but I need that region color-coded so that I can refer to the cytosol/intracellular area in captions. Do you have any suggestions for an alternate contrasting color? Seppi333 (Insert 2¢ | Maintained) 02:11, 1 March 2014 (UTC)[reply]
Much improved! I unfortunately do not have time at the moment to go into detail (moving house), but I might have time later to go over it again. Removed my oppose, but to support I have to make sure it's all in order. Great work! Mattximus (talk) 21:27, 4 March 2014 (UTC)[reply]
* Would it be easy to move the amphetamine which is diffusing across the membrane (I did not know that!) from the lower left to the right of the axon terminal. The reason is that all points of entry for amphetamine should be together and there is already a second entry point on the bottom right. Presumably this diffused amphetamine could also go to the TAAR1, but you would need to confirm that. Mattximus (talk) 19:50, 7 March 2014 (UTC)[reply]
  • This figure from the Miller paper covers/cites about 2⁄3 of the content in the diagram above (VMAT2 not included).
  • The references listed below can be viewed or downloaded on this page. Seppi333 (Insert 2¢ | Maintained)

References

  1. ^ a b c d Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.
  2. ^ a b Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Ann. N. Y. Acad. Sci. 1216: 86–98. doi:10.1111/j.1749-6632.2010.05906.x. PMID 21272013. VMAT2 is the CNS vesicular transporter for not only the biogenic amines DA, NE, EPI, 5-HT, and HIS, but likely also for the trace amines TYR, PEA, and thyronamine (THYR) ... [Trace aminergic] neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC).
  3. ^ Offermanns S, Rosenthal W (2008). Encyclopedia of Molecular Pharmacology (2nd ed.). Berlin: Springer. pp. 1219–1222. ISBN 3540389164.

Not Promoted --Armbrust The Homunculus 03:36, 8 March 2014 (UTC)[reply]


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