Talk:Orexin

How

How many amino acids in orexins? Molecular weights of the peptide? —Preceding unsigned comment added by 12.158.118.18 (talk) 18:23, 28 December 2007 (UTC)

ÁReferences, e.g. on the discovery of orexins, would be nice. JFW | T@lk 11:00, 14 July 2005 (UTC)

Well you should have added some then. It took me all of two minutes to find a suitable reference on the web. -- Derek Ross | Talk 17:33, 14 July 2005 (UTC)

Well, great. Thanks for doing a {{sofixit}} on me! JFW | T@lk 18:41, 14 July 2005 (UTC)

My goodness! I didn't know about that one. It seens that there's a template for everything nowadays! -- Derek Ross | Talk 22:37, 14 July 2005 (UTC)

Sofixit is really nice when an anon complains on the talk page about his/her favourite theory or subject being underrepresented. To look more legitimate, it may be advisable to {{sofixit}}. JFW | T@lk 23:45, 14 July 2005 (UTC)

Thank you for the article, I have learned what I wasn't aware of about Orexin A.

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Article is a little heavy on the feeding/metabolism side which may be overplaying the role of orexin. Primarily seems to be important in regulating sleep/wake transition and maintaining high alertness, not so much involved in general arousal or ingestive activity.

Also would be good to ensure that either both names are used at all times or that one name is used consistently. Switching between orexin and hypocretin in the same paragraph is distracting. Until the literature settles on one name we should use both. Personally I strongly dislike hypocretin (hard to abbreviate, for one thing - OXA vs. HCRT-1 saves three keystrokes every time I type it) but think it is appropriate to include the name here. As article is titled "orexin" I placed this name first in all instances. -DrNixon 08:20, 1 February 2006 (UTC)

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I don't think it's fair to say that the primary role of the orexins is either sleep/wake regulation or appetite regulation, or anything else at this point. Given the presence of long-form leptin receptors on orexin neurons, their coexpression with dynorphin in lateral hypothalamic neurons, and their connectivity with NPY neurons in the arcuate nucleus and lateral hypothalamus, I think it's fair to say that appetite regulation/ingestive behavior is not merely an incidental effect of the orexins. Many neuropeptides perform several functions. Is it fair to describe a single function as the primary function? I have studied other functions of the orexins besides sleep/wakefulness and appetite regulation, and I believe there is great potential for many other functions to be revealed.

As one who has administered orexin-A centrally to both rats and mice, I believe you are mistaken about arousal. We haven't published our data concerning arousal per se (it's not what we were studying), so all I have is my word, but mice are very much aroused beyond simple wakefulness upon central delivery of orexin-A. (Wang et al have reported increased spopntaneous activity in orexin-A-treated rats with free access to running wheels.) This might simply be a pharmacological effect, but it does point toward an endogenous role for orexins in arousal.

Also, in reference to the above comments on the discovery of the orexins, I think a reference to "clone 35" by Gautvik et al is in order. I'll get on it. Dcs002 (talk) 10:13, 20 September 2009 (UTC)

Great to see somebody with expertise contributing to the article! Please don't go beyond the published literature, though, even if you know it's wrong. This can be pretty frustrating -- I know it is for me concerning my own area of expertise -- but we have to stick to it or else we'll have statements in articles that other people have no way of verifying. Regards, Looie496 (talk) 23:18, 20 September 2009 (UTC)

Thank you for your comments, and thanks to everybody who cares enough about neuroscience to take the time to share your insights! What a marvelous creation this Wikipedia is! :o)

I would never publish my own observations on the article page unless they were in the research literature. I think my point was to give people here on the discussion page a pause to think about characterizing the orexins as "not so much involved in general arousal." I'm not aware of that conclusion appearing anywhere in the literature, and personally I've seen evidence to the contrary. I don't think there's any real definitiveness to the point of endogenous arousal just yet, though I admit I've fallen far behind in my literature reading. I actually wrote my doctoral thesis on the appetitive effects of orexin-A in 2002, and I did further work with it in 2005-06, but once that work was done my attention turned elsewhere. Dcs002 (talk) 06:16, 21 September 2009 (UTC)

WikiProject class rating

This article was automatically assessed because at least one WikiProject had rated the article as start, and the rating on other projects was brought up to start class. BetacommandBot 16:30, 10 November 2007 (UTC)

Nympholepsy?

Could someone do a text search in the article for "nympholepsy" and check if the usage is appropriate? or was it intended to be "narcolepsy"? According to a online dictionary, "nymplolepsy" means "an emotional frenzy" 137.92.97.114 (talk) 03:10, 30 December 2007 (UTC)

I'm pretty sure that the editor meant narcolepsy. I'll make the change. -- Derek Ross | Talk 03:27, 30 December 2007 (UTC)

Agonists and antagonists

Would it be useful to explain to the reader that peptides don't have much practical value as treatments because they can't cross the blood-brain barrier? Looie496 (talk) 00:05, 7 October 2008 (UTC)

No, I would strongly recommend against posting such an opinion. Work has been done, primarily by William Frey and his lab group in St. Paul, MN, and Scott Panter at the VAMC in San Francisco, CA, that demonstrates a method of delivering neuropeptides intact via the intranasal route. Human studies have been proposed using specially designed vortex nasal spray devices to bring the peptides in contact with the olfactory epithelium (though at least one human study reported in the research literature used an electronic atomizer). The peptides are then transported directly, via the olfactory and trigeminal nerves, to the brain, and widely distributed from the olfactory bulb backward and from the pons forward. The blood-brain barrier simply doesn't exist where the olfactory nerves contact the olfactory epithelium. This method has been used in mice and rats for some 15 years now with many peptides and other large molecules.

Several human studies showed functional improvement in patients with Alzheimer's disease or mild cognitive impairment (MCI, a precurser of Alzheimer's disease) following intranasal insulin administration (Neurology. 2008 Feb 5;70(6):440-8. Epub 2007 Oct 17 and BMC Neurosci. 2008 Dec 10;9 Suppl 3:S5, others) and one other compound that I think is still confidential. (I am affiliated with that research group, and I signed a confidentiality agreement concerning their unpublished work.) The functional improvement in Alzheimer's patients is HUGE NEWS, because it's the first time ever that a treatment has been found to improve function, as opposed to simply slowing down the degenerative process. In the case of insulin, it is believed by the investigators that the known "nerve growth factor" function of central insulin is actually working in the brain to repair some of the damage caused by AD.

A quick look at PubMed shows that oxytocin, MSH/ACTH4-10, vasopressin, NAP, TRH, and possibly other peptide substances have been delivered to humans intranasally, mostly with functional effects.

ALL OF THIS has been done by delivering peptide molecules directly to the human brain via the intranasal route. Animal testing using intranasal orexins has begun, but we haven't yet published anything.Dcs002 (talk) 07:13, 21 September 2009 (UTC)

Point taken. I was actually aware of the oxytocin work but somehow didn't make the mental connection. It would be nice to get an article on intranasal administration of drugs that would give an overview of these techniques. Regards, Looie496 (talk) 16:56, 21 September 2009 (UTC)

Oh my, I didn't even think to look if that page existed. I'll start one sometime soon if no one else does. I'm fairly current with that literature. Dcs002 (talk) 01:13, 22 September 2009 (UTC)

That would be excellent. Cheers! Oh, and welcome to Wikipedia! -- Derek Ross | Talk 05:02, 22 September 2009 (UTC)

Problem: "Intranasal route" apparently had a page until last March, when it was merged with "insufflation." I think this was a mistake on many levels. My reasons for this opinion are posted on http://wiki.riteme.site/wiki/Talk:Insufflation#Merger_proposal I don't know what to do right now. I believe the page needs to be made, but I don't know what to do in light of the existing redirect and the consensus that was made before I was aware of the discussion. Any suggestions? Dcs002 (talk) 10:52, 25 September 2009 (UTC)

Oh heck, let's make this even more confusing. I just found a page called Nasal_administration. Now I'm even more confused! Dcs002 (talk) 10:54, 25 September 2009 (UTC)

Insufflation is clearly the wrong article for this stuff, but is there a major problem with the title "nasal administration"? Looie496 (talk) 17:32, 25 September 2009 (UTC)

I don't have a huge problem with "nasal delivery," but I think it should be "intranasal" to be correct. I've put that out on the Nasal_administration discussion page along with my reasons. Someone on the discussion page for Insufflation changed the redirect to the Nasal_administration page, so that's where I'll take this whole thing. Thanks for your help Looie! Dcs002 (talk) 15:47, 26 September 2009 (UTC)

Nicotine addiction

See Paul Kenny's article in the online Early Edition of the PNAS for the week of November 24, cited in Scientists find blocking a neuropeptide receptor decreases nicotine addiction LeadSongDog (talk) 20:01, 25 November 2008 (UTC)

Interesting. -- Derek Ross | Talk 20:28, 25 November 2008 (UTC)

Wow, thanks for the link. This kinda surprises me. (I am behind on my reading!)

Effect on thyroid hormones

Can anyone clarify/confirm/deny the hypocretin effect on thyroid hormones suggested by www.naturalnews.com/025325.html  ? "... hypocretins are wired to many different aspects of nerve function. They provide input to the primary department in the hypothalamus gland that controls the production of TRH (thyroid releasing hormone), which has control of the pituitary (which makes TSH), and thus has overall control of thyroid hormone production. The message hypocretins deliver is as follows, "We are in a state of high stress alert wherein our brain must remain hyper-vigilant, however, to conserve fuel so we don't perish, turn down the production of thyroid hormone in the rest of the body (a self preservation strategy, especially during times of famine or infection).""

Some data at "Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men " but I'm not sure if it's too specific to a disease state. Rod57 (talk) 11:23, 16 January 2009 (UTC)

I looked at either TRH or TSH (can't remember which now) in a few rats after chronic orexin-A administration into the lateral hypothalamus, and I found no effect on whichever of those two I tested. It was in the late 1990s, so my memory is foggy. We didn't pursue it any further. Dcs002 (talk) 07:19, 21 September 2009 (UTC)

History and nomenclature

I just added discovery of receptors, clarified authorship of Sakurai and colleagues, referenced clone 35 in the 3rd paragraph, and removed "dispute" from 4th paragraph.

Ever since the infancy of this article, the name Masashi Yanagisawa has been featured prominently, and I've wondered if he or someone in his lab had been editing this page to hail him as the sole discoverer of the orexins. The convention is usually that the first author of the paper is the first name credited with the contents of the paper. Many years ago I switched the reference from Masashi Yanagisawa (no "et al" or "and colleagues" at the time, just him) to Sakurai and colleagues, and I added the reference to de Lecea and colleagues, but within a few days my changes were erased and Yanagisawa was again hailed as the sole discoverer. And it's not just his name, it's Masashi Yanagisawa at the University of Texas Southwestern Medical Center at Dallas. No one else's affiliations are named in this article, and I'm not sure how appropriate it is. And until I inserted the reference to Gautvik and clone 35, Yanagisawa's name was always the one that appeared first, though that group's paper was actually the third to be published on these peptides.

I've always thought that Gautvik and colleagues and de Lecea and colleagues (same group really) should get the lion's share for the discovery of these peptides because a) they first identified clone 35, b) their work published in 1998 was a continuation of their earlier published work, which I think establishes them as the pioneering lab group, and c) well, their paper was published before Sakurai and colleagues, albeit only a month (which is really considered to be the same time). Sakurai and colleagues deserve a great deal of credit for the thoroughness of their description of the peptides, getting the exact sequence correct, describing one function (feeding) of these peptides, and most of all for discovering the receptors. (Maybe I'm also driven by what I perceive as the promotional nature this article has historically had in regards to Yanagisawa.)

The reason I removed the word "disputed" from the fourth paragraph is that I believe it connotes a sense of animosity that doesn't exist. Researchers simply publish under whichever name they prefer, being sure to mention the other name, and everyone seems to be waiting too see whether the field decides on one name or the other. That's the attitude I've seen at conferences anyway. Yes there are reasons given on both sides why the name should be one or the others, but these are more like competing proposals than a subject of real dispute. Dcs002 (talk) 07:01, 24 September 2009 (UTC)

As you of course know, the last author is frequently the person who designed and managed the work, but I completely agree that the usual way of citing the work would be either "Sakurai et al" or "the laboratory of Masashi Yanagisawa"; just plain "Masashi Yanagisawa" is misleading. Anyway, it looks like the reference dates back to the very first version of the article in 2003, and probably was based on a press release, since the editor who created the article doesn't seem to focus much on biology of any sort. Regards, (and remember to sign your talk page messages!) Looie496 (talk) 00:17, 24 September 2009 (UTC)

I have updated the nomenclature paragraph to recognize a nomenclature compromise. Having hypocretin refer to the gene and orexin refer to the peptide/proteins is reflected in GenBank database searches and the IUPHAR database or Guide to Pharmacology. That being said, individual authors and labs will probably continue to refer to orexin/hypocretin by whichever name suits them. 08:06, 7 September 2015 (UTC) 149.171.66.108 — Preceding unsigned comment added by 149.171.66.108 (talk)

Removed reference to criticism of the use of the term 'orexin' because the feeding may be incidental to general arousal. That comment did not have a citation and a paper that might be relevant (Ida et al 1999) actually follows the orexin nomenclature. — Preceding unsigned comment added by 149.171.66.108 (talk) 06:25, 3 October 2016 (UTC)

External links

Why is there a link to CIMIT in this section? Is it here for a purpose other than garnering publicity for the organization? I think it should be removed. Dcs002 (talk) 09:47, 9 October 2009 (UTC)

Brown fat activation

The orexin article says: "Hence obesity in narcoleptic patients may be due to orexin deficiency leading to brown-fat hypo activity and reduced energy expenditure." This is, however, impossible because adult humans do not have brown fat. — Preceding unsigned comment added by 141.20.48.39 (talk) 10:01, 5 June 2012 (UTC)

That's not actually true. Adult humans have less brown fat than children but they still have some, mostly in their upper chest and neck. See our article on Brown fat for pictures. -- Derek Ross | Talk 22:13, 6 June 2012 (UTC)

Structure & Content Suggestions

Narcolepsy is mentioned several times before it is defined under “wakefulness.” I would suggest to either define it (or describe it) earlier in the article or just hyperlink it for people to read about it themselves. I also think the last paragraph under “wakefulness” can be categorized under a different heading. It does not directly relate to wakefulness, but is useful because it is talking about the problems that can occur if one does not have orexin-producing neurons. Under ‘food intake,’ why does orexin increase the craving for food? You could tie this in with the increased obesity rate for those with low levels of orexin. The ‘energy metabolism’ section could be expanded or even grouped with the ‘food intake’ section.

Overall, the article was very informative and had a lot of good content! Cbruha11 (talk) 15:19, 28 March 2014 (UTC)

If higher levels of orexin correlate with improved mood and less depression, but also greater wakefulness, then how could orexin explain higher incidence of depression in narcoleptics? If anything it would suggest to me that narcoleptics should have lower incidences of depression, which the page doesn't read to suggest. Scuriusx86 (talk) 23:55, 10 November 2015 (UTC)

Well, just a guess but narcoleptics are possibly more prone to depression owing to the difficulty of moving forward with their lives caused by sleeping and cataplexy. It may well be that orexin makes them less depressed than they would otherwise be and yet does not have enough of an effect to cancel out the negative feelings caused by that frustration. -- Derek Ross | Talk 07:49, 11 November 2015 (UTC)

Orexin A of greater importance?

It's been a while since I visited this page, but I just noticed this: "Studies suggest that orexin-A may be of greater biological importance than orexin-B." I know I've been away from orexin research for a long time now, but on its face this statement seems preposterous. First, the fact that orexin-B has been observed as less potent or less effective than orexin-A at anything only means we don't know if its main endogenous function is to do something we haven't thought to test. Orexin-A is clearly more effective at inducing feeding. Does that make it more biologically important? We don't know what we don't know here. We don't know all of the possible functions of these peptides. Second, when I was studying the orexins (which ended in 2006), orexin-A had simply been studied more than orexin-B. We knew more about it, so researchers had a lot more to build on, and therefore a lot more was published, building a clearer picture of its function in the brain. It was more effective at inducing the effects that we were looking for, but we have no idea what all of its effects are. We can't know that for any neuropeptide until we figure out exactly how the human brain works. Third, importance is a vague and dependent statement of a thing's value, and is nearly a meaningless thing to say on a scientific level. Scientists speak in specifics. Important for what? Appetite? Arousal? Memory? Important how? Activation? suppression? Survival under extreme conditions? The fact that orexin-B is preserved across so many species is compelling evidence of its evolutionary importance. We either need to source that claim or get rid of it. Dcs002 (talk) 11:07, 24 May 2014 (UTC)

I agree. Orexin-A is certainly the go-to peptide for agonist-based studies and the OX1 receptor has got more selective antagonists for it, but that doesn't mean that OX-B or the OX2 receptor doesn't do anything. I have therefore removed that sentence. (149.171.66.108 (talk) 06:29, 3 October 2016 (UTC))

Influenza vaccine

We should probably add the epidemic (1,300 cases) of narcolepsy in Europe caused by the Pandemrix influenza vaccine, which triggered an autoimmune reaction to hypocretin receptor 2. An exposed region of the influenza nucleoprotein A shared residues with a fragment of the first extracellular domain of hypocretin receptor 2. People with HLA-DQB1*0602 haplotype developed protective immunity to influenza and an autoimmune reaction to hypocretin receptor 2, leading to death of the cells and incurable narcolepsy. There were 1,300 cases out of 30 million doses of Pandemrix, so it's a relatively rare reaction, on the order of the other known, rare risks of influenza vaccines.
Ahmed SS,Volkmuth W, Duca J, et al.
Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor
http://stm.sciencemag.org/content/7/294/294ra105
Science Translational Medicine. 01 Jul 2015; 7(294):294ra105. DOI: 10.1126/scitranslmed.aab2354

Gretchen Vogel
Why a pandemic flu shot caused narcolepsy
http://news.sciencemag.org/health/2015/07/why-pandemic-flu-shot-caused-narcolepsy
Science. 1 July 2015 DOI: 10.1126/science.aac8792.

And Science calls it hypocretin. Is that the name now? --Nbauman (talk) 03:15, 6 July 2015 (UTC)

Both names are still widely used in the literature -- orexin a bit more widely, I think. Regarding the vaccine, it might be reasonable to add a paragraph on that story. Looie496 (talk) 15:39, 7 September 2015 (UTC)

Housekeeping

I'm not a specialist in this area, but it does appear that the clause, "but immunocytochemistry tactics revealed the various projections this area truly had to other parts of the brain. " from the second paragraph of the Discovery section needs some kind of verb.

..had to connect...???

I'm hoping that someone can add the right verb. — Preceding unsigned comment added by Joel1947 (talk • contribs) 17:11, 29 July 2017 (UTC)

Edit War

High plasma triglycerides (from a high fat diet) and low blood sugar (hypoglycemia) increases orexin levels, which increases appetite through orexin-stimulated neuropeptide Y action. A high fat diet more than a high calorie diet has been shown to increase obesity and orexin release.

References

The poorly sourced content needs to be re-added with a review. Not primary sources. Please with WP:Primary and WP:3RR. Petergstrom (talk) 17:59, 3 February 2018 (UTC)

These are biomedical claims and therefore need secondary sources to support them. Here are a couple of possibilities:

• Imperatore R, Palomba L, Cristino L (2017). "Role of Orexin-A in Hypertension and Obesity". Current Hypertension Reports. 19 (4): 34. doi:10.1007/s11906-017-0729-y. PMID 28353077. Orexin and Obesity (page 34)
• Goforth PB, Myers MG (2017). "Roles for Orexin/Hypocretin in the Control of Energy Balance and Metabolism". Current Topics in Behavioral Neurosciences. 33: 137–156. doi:10.1007/7854_2016_51. PMID 27909992. Section 13: OX and the Control of Glucose Homeostasis
• Xu TR, Yang Y, Ward R, Gao L, Liu Y (2013). "Orexin receptors: multi-functional therapeutic targets for sleeping disorders, eating disorders, drug addiction, cancers and other physiological disorders". Cellular Signalling. 25 (12): 2413–23. doi:10.1016/j.cellsig.2013.07.025. PMID 23917208. Orexin signaling in feeding, energy homeostasis, obesity and diabetes

Boghog (talk) 18:29, 3 February 2018 (UTC)

Thanks Boghog - is it ever the case that a 'citation needed' or 'better source needed' tag can be added.--Iztwoz (talk) 18:37, 3 February 2018 (UTC)

The above primary sources are both animal studies and the accompanying text implies that results of these studies may also apply to humans. This is not acceptable per WP:MEDANIMAL. One would need to modify the text to state that these are animal studies. Boghog (talk) 19:31, 3 February 2018 (UTC)

Wiki Education assignment: Adv Molecular Bio Bass-FSU-Fa23

This article was the subject of a Wiki Education Foundation-supported course assignment, between 28 August 2023 and 15 December 2023. Further details are available on the course page. Student editor(s): Adn23 (article contribs). Peer reviewers: Achait2023.

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