Talk:Norepinephrine transporter

This page is currently being expanded by a group students from Dr. Burdo’s Intro to Neuroscience (BI481) at Boston College as part of our assignment to edit a Wikipedia neuroscience stub. The group working on this page consists of Marielle Daclan, Allison Weiffenbach, and Mathew Thomas. Any comment or suggestions regarding our additions and alterations would be greatly appreciated. --Mdac927 (talk) 18:12, 3 November 2011 (UTC)

Non-peer review

Hey guys, you have done a really great job expanding this stub. You have reached a C rating which is really great as well. It looks like you guys are basically done, my only suggestion is to try and find a picture that you can use for the structure. You can usually find images on PDB, but I'm not sure what the copyrights are like on those images. If you haven't looked at Wikimedia Commons yet, you should definitely do that. Also you could contact the group that is doing Cyclic nucleotide-gated ion channel, I think they were able to get a picture of the structure. Otherwise, great work.
Good luck! 136.167.123.243 (talk) 21:50, 5 December 2011 (UTC)

Hey Abby, I've searched many times but there's nothing available on WikiCommons on NET except for the graphs that were already present on the original stub. I also just looked on PDB but nothing seems to come up on NETs. There is actually only one picture of it that I've seen in a paper thus far but I believe it's copyrighted. Also, I think that rating was there before we started editing. I'm considering seeing if my group will upload an original picture of the transporter structure that is "professional looking," but based on my computer skills, I don't know if we will be able to do that. Thanks for your input! Mdac927 (talk) 22:47, 5 December 2011 (UTC)

I just added my own image for the structure of NET. Mdac927 (talk) 22:37, 6 December 2011 (UTC)

Peer Review

Hi guys! This was a great article! I loved the use of so many images, they were extremely helpful in visualizing the transporter. The only confusion I had with the images were the graphs in the first table next to the contents box. If you could maybe explain the significance of those that would be helpful. Also under Transport Mechanisms I'm not sure if Na&2B and Cl%2B are supposed to be formatted that way or not. also you guys did a great job of making sure there were a lot of links throughout your article; maybe also include links for serotonin and GABA transporters. Finally instead of linking Orthostatic intolerance, Depression, ADHD, Schizophrenia, Cocaine, and Amphetamines as main article maybe link them within the paragraphs underneath the heading instead? Other than that great job! Zonfrell (talk) 05:03, 15 November 2011 (UTC) Lexi

To be honest I wasn’t really too sure about those graphs either at first, but they were in the original stub and we never removed it. From what I can understand it’s a simplified version of the pattern of the norepinephrine transporter gene expression in various areas of the body. The graph is clearer if you click on the images because that expands the x and y labels.

I’m not sure what Na&2B and Cl%2B is supposed to be but I’ll ask the group and figure it out.

I didn’t even realize I missed those two. Thanks for pointing them out! I just added in links to serotonin and GABA transporters.

For the main article links, I put them in there because although a normal internal link would also lead to the main article, I wanted to make it clear that even though this specific section is about cocaine, for example, there is a much more expanded article that the reader could reference if they wanted to know more since our cocaine section only relates to the norepinephrine transporter. Thanks so much for your input! It was really helpful. Mdac927 (talk) 17:34, 17 November 2011 (UTC)

Peer Review 2

I enjoyed the article very much especially the Structure and Function sections and the Therapeutic Potential section. Both of these were concise and clearly written. The ideas within these sections were presented in a way that was easy to follow and informative. I thought for the most part you guys did a good job identifying terms to wiki link to, however I thought a few more terms would have been helpful, especially if they are important to understand a significant fact within the article. For example terms like reuptake and exon. Other than that only a couple of minor thoughts I had about the article. In the section titled transport mechanisms you might have a typo when the co-transported ions are brought up. In Regulation, you state PKC is a secondary messenger and I'm not sure it is a secondary messenger itself, but rather it is affected by secondary messengers. The article gets really in depth when Single Nucleotide polymorphisms are discussed and I'm not sure that measure of explanation is needed for them. Wiki-linking might be enough for that. However, if you are going to examine SNP's in depth it might be a good idea to give information about what the numbers they have mean (ex: rs11568324 or Thr99Ile). Also in some of the middle sections some simpler wording could be used instead of jargon (ex: Wild-type version of a gene could just be referred to as the normal version). Finally the title of the Therpeutic Potential might be a little misleading, as NET's are the target of drugs.Baumannd (talk) 22:58, 15 November 2011 (UTC)

I added links for reuptake and exon. I’m also glad you mentioned that about SNPs because I thought it was a little too long also. I do think that SNPs are very important and should be discussed briefly within the article, so I just I shortened it a little. For the SNP nomenclature, I just looked into it and “rs” stands for RefSNP, meaning it is in the database at the National Center for Biotechnology Information (NCBI). The numbers that follow are its ID number. While this information is useful, I don’t think it would flow if I added it in the article. Rs11568324 is essentially just a name for a particular SNP. As for the other notation you mentioned, Thr99Ile, I think because it is included in the table it could use some clarification as to what it means so I added an explanation in the caption. I also added a link to “wild type” to clarify what it means. I also agree about “Therapeutic Potential.” I’ve changed it to “Therapeutic Uses.” Mdac927 (talk) 19:13, 17 November 2011 (UTC)

Peer Review 3

This article was very interesting and was organized really well. An aspect that I really that was great about this article was the links to the other wikipedia articles underneath the titles of the individual sections. If anyone did not understand what was said in a certain section, they can just click on the link to the other article for a more thorough explanation. The whole article flowed very nicely and the usage of the images made it even easier to understand. I only have a couple of suggestions. You really only need to wiki-link a certain word only once: the first time you mention it in the article. For example, norepinephrine was wiki-linked multiple times throughout the article. You may also want to bold "norepinephrine transporter (NET)" in the very first sentence. It seems that every Wikipedia article tends to do this for whatever subject it is discussing. Other than those two points, I think your article is almost perfect. Keep up the great work! (Colehawk92 (talk) 04:58, 16 November 2011 (UTC))

I get what you’re saying about over-linking norepinephrine. However, I think linking to something multiple times throughout the article is okay as long as it’s once in a different section, since I think some readers may only read certain sections and not the entire article. I went through and removed whatever redundant links I could find. Also, NET is now bold in the introduction thanks to another Wikipedia contributor. Thanks for your input! Mdac927 (talk) 19:28, 17 November 2011 (UTC)

Peer Review 4

Only the acronym DAT is used. You may want to spell it out and put the acronyms in parenthesis, so next time you use DAT people will know exactly what is being referred to. Also, under 'Norepinephrine', there is a sentence that says "Dysregulation of removal of norepinephrine by NET is associated with many neuropsychiatric diseases." Maybe you want to elaborate what the diseases are. There is an introduction sentence under 'Therapeutic Potential'. Maybe you can mention these disorders after your sentence under 'Norepinephrine'. Under 'Transport Mechanisms' you write Na&2B then Na%2B afterwards. I'm not sure if this is intentional, but I really can't understand what these mean, so if you elaborate, it might be helpful. Also, maybe you can internally link ligand gatd channels or explain what it is. If it was my first time coming across that word, I wouldn't know what it means. Then, under 'Depression' you write medications results in higher extracellular concentrations of NE and that this longer remaining in the synapse allows it to reach normal levels. How is this possible if the medication results in higher extracellular concentrations? Also, under 'ADHD', you only talk about the drug atomoxetine, but what about other drugs? What are some side effects of others drugs and what is the main difference between atomoxetine and drugs like adderall? It should be made clear why you chose to talk only about atomoxetine. (ie. Only atomoxetin affects NET transporters.) Finally, under 'Schizophrenia' the fifth line states, "that were hidden away in their homes." I think the that should be they. Please check grammar. Overally, the article was well thought out and interesting to read. Stephanie Lee (talk) 03:09, 16 November 2011 (UTC)

Hi Stephanie- Thank you for the advice. The corrections you gave were very helpful. In regards to the Na%2B correction, that was a typo and it should have read Na+ (same with Cl-). In regards to your recommendation to elaborate on the neuropsychiatric diseases, i added "discussed below" rather than describing them there. I didn't want the article to become repetitive. But I agree that something needed to be added so the reader knew we went into more detail on the diseases. Thank you for your help! (talk) 14:02 7 December 2011

Stephanie,

Normally, the NET functions by transporting the neurotransmitters out of the cell, so if the reuptake medications inhibit the NET, then the neurotransmitters that would normally be taken out side the cell would be trapped inside the synapse. It did not make sense that the extracellular concentrations would be higher during the NET blockade, but it is true that the normal function is inhibited and that the NT levels increase, ultimately stimulating the presynaptic neuron. I am not sure if you read further into the ADHD section, but I had also mentioned other drugs like Methylphenidate and Vyvanse and their corresponding side effects. However, I edited the first sentence, cluing in on that I was going to talk about the other drugs besides atomoxetine. Thanks for your help! (talk) 20:54 7 December 2011 —Preceding undated comment added 01:54, 8 December 2011 (UTC).

I moved the previously listed ADHD drugs to the beginning of the ADHD section, now mentioning that these drugs affect both dopamine and norepinephrine transporters. It is more clear that atomoxetine was covered in more detail because it specifically targets the NET. Mdac927 (talk) 05:00, 8 December 2011 (UTC)

Peer Review 5

Hello NET group! I first wanted to say that this article was superbly detailed, and I can see that a lot of research and attention went into writing this article. That being said, I only have minor suggestions to improve on, mostly grammatical or formatting issues or further clarifying a point:

Consider formatting "Na +/Cl --dependent" differently in the second sentence, perhaps written as "sodium-chloride" and then the abbreviation in parentheses (Na +/Cl -) afterward. For us science majors, we instantly know what Na and Cl stand for, but we shouldn't assume that all the readers who see this article will know that. And for the RNA expression pattern, it might be helpful to provide a brief caption to explain what exactly we are looking at.

One of your sentences reads "The reuptake of these two neurotransmitters is essential in regulating concentrations in the synaptic cleft." But it might be clearer if written "The reuptake of these two neurotransmitters is essential in regulating their concentration in the synaptic cleft."

Also, in the sentence "NE, or noradrenalin (NA), has an important role in controlling mood, arousal, memory, learning, and pain perception" I am pretty certain that you mean to say Ne is the same as NA, but might you want to word it something like "NE, also known as NA" or something that clarifies this point? And just a small typo in the sentence "In addition, any antidepressants and recreational drugs compete for the binding of NET with NE. [3]" where I believe "any" should be "many."

I'm sure this was another formatting issue, but "Na&2B and Cl%2B" under Transport mechanisms was probably supposed to read Na+ and Cl-. Could you explain a little more on what you mean by "The ion gradients of Na%2B and Cl%2B make this reuptake energetically favorable" -- at least explaining to readers the relative positive to negative gradient existing inside and outside of the cell?

The "NET Gene" section was very well explained and makes some very difficult terminology relatively easy to understand and follow, even when simply explaining the difference between nonsynomymous and synonymous cSNPs. The table of missense mutations was also nicely formatted and clarified the text that preceded it.

I saw very thorough work done and sold statistics, like "90% of the norepinephrine released will be taken back up in the cell by NET," included in the Structure and Function section. The topics covered in the "Therapeutic Potential" section were very interesting reads, and I thought there were great explanations of linking the disorders with the role of NE and NET. Under the Depression heading, I would just spell out "united States" in the sentence "However, currently far more potent drugs have been developed in the US."

If you can find an image, maybe include one that shows the synaptic cleft with an NET and its associated neurotransmitters? I think one of those typical textbook images would be okay. Again, this was very impressive work! Aeri Alexander (talk) 11:51, 16 November 2011 (UTC)

Thank you for your advice! I agree with most of the corrections that you made, and fixed the areas that you thought were unclear or could use more work. In regards to the suggestion about a picture, we decided to add an image of the norephinephrine transporter. Although it is not in the synaptic cleft, I think it would be repetitive to have a similar image again in the article. Thanks again! (talk) 14:15 7 December 2011 (UTC)

You made a good point about the sodium-chloride abbreviation. I changed it. As far as the RNA expression graph goes, it does not seem to work as a normal image where I can easily add a caption. From what I could find, the table was constructed using a "geneid" on Wikipedia and is under the control of User:ProteinBoxBot. This already existed on the stub when we began editing. Readers can click on the thumbnail and an enlarged graph appears with labels. Mdac927 (talk) 00:39, 8 December 2011 (UTC)

Peer Review 6

This is a fantastic page! Like others have said, it is informative and the flow of your page is logical and easy to follow. I would suggest making links to the acronyms, especially in the first paragraph of the structure and function page.

There are also the minor changes needed for the things like "Na%2B and Cl%2B". I also personally found how the paragraph under "location in the nervous system" was worded to be a little confusing, but that could just be my limited knowledge of the subject. This could be fixed by possibly just adding a few more link, or even possibly a picture that illustrates the differences between the locations.

Your gene section is really impressive. I especially like your chart. You guys do a great job of summarizing and taking out the necessary information that relates to your topic under Orthostatic intolerance.

Under the depression article you say "These medications prevent NET from functioning normally, resulting in higher extracellular concentrations of NE. " If a person is depressed doesn't that imply that that there is something wrong to begin with, so aren't the drugs working to help NET function properly? Also, "However, dopamine in most brain regions is cleared primarily by the dopamine transporter, which works roughly ten times faster.[18] " doesn't really connect with the rest of the paragraph, it needs to be followed by a statement about what this means in terms of the affects drugs have.

The ADHD section is really informative but is more about the drugs available now than their effect on the NETs. I think its really interesting, but I'm not sure if it actually fits in with the rest of the article. The same could be said for the Schizophrenia section but it is still interesting and maybe could be expanded later, or could be condensed and mixed into the SNP section where you initially mention these things.

Under Cocaine, you might want to consider rewording this: "known to be one of the best-known drugs of substance abuse". The rest of the information on drugs is done excellently.

Overall this is really good and very informative article and its clear you guys have done a lot of work, so congrats and good luck. Gallagcw (talk) 00:12, 17 November 2011 (UTC)

Thank you for your advice! I made corrections to some of the format/grammar mistakes that you mentioned. I tried to clarify the paragraph about location in the nervous system. I couldn't find a picture that would illustrate the difference in locations, so I hope that by editing the paragraph it is less confusing and does not require a picture. (talk) 14:23 7 December 2011 —Preceding undated comment added 19:23, 7 December 2011 (UTC).

Thanks for your insightful suggestions! I reread the sentence about the NET’s role in depression and you were right about it not making sense. The NET is responsible for transporting norepinephrine and other neurotransmitters out of the synapse and therefore decreasing their concentrations in the synapse. When it is blocked by a reuptake inhibitor, the neurotransmitters are instead trapped inside the synapse making the cell response to be more excitatory. I added more information to the ADHD section just to explain how the NET is involved in causing ADHD. It is similar to the role it plays helping to alleviate the symptoms of depression. I could not find a lot of information on the role of NETs in causing schizophrenia because not much research has been devoted to figuring out the mechanism by which it is caused. Also, I included the drugs that are used to combat each type of psychiatric disorder because of its classification under “Therapeutic Uses.” (talk) 19:55 7 December 2011 —Preceding undated comment added 00:56, 8 December 2011 (UTC).

For the schizophrenia section, I added in a part about studies relating schizophrenia to the impaired regulation of NE. Also, I don't think it belongs under "Therapeutic Uses" because no medications that treat schizophrenia by directly targeting the NET are mentioned, so I moved this section under "Further Research" and associated the ADHD and schizophrenia sections more with NET than just available drugs. Mdac927 (talk) 02:44, 8 December 2011 (UTC)

Peer Review 7

Great intro! It gave a clear overview of the article. For the section "Norepinephrine," a link to or a brief definition of the word "noradrenergic" would help. Also, the sections "Clinical Significance" and "Therapeutic Potential" seem like they can be joined under one heading. The pictures were great, but another simple picture of what NET looks like, or at least where it is located in the synapse, may be useful. Overall, the article was very thorough and I can't think of anything it lacks, but a brief section on how NET was discovered may be helpful if you're thinking of expanding. Choino (talk)

I changed the name of “Therapeutic Potential” to clear up some confusion, so now the two can be distinguished, since this section is about conditions with drug therapy that target the norepinephrine transporter and “Clinical Significance” has to do with orthostatic intolerance being linked to a mutation in the gene. I’ve tried searching for a picture of the transporter but there are no available images on Wikicommons but that would definitely add to the article so I'll try to see what I can do about that.Mdac927 (talk) 02:32, 18 November 2011 (UTC)

I just added a picture of the NET structure. Mdac927 (talk) 22:39, 6 December 2011 (UTC)

Location?

This well put together & deatailed article says, "NETs are located away from the synapse, where norepinephrine is released. They are found closer to the plasma membrane of the cell." (italics mine) But mustn't they be ON the plasma membrane in order to function for reuptake? And how far away from the synapse are they, and is it normal or unusual for reuptake transporters to be other than close to or in the synapse? I see from Wiki Monoamine_transporter (MAT: SERT, DAT, NET) that, "MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron." UnderEducatedGeezer (talk) 04:28, 3 October 2016 (UTC)