Orexins
| Orexins | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 33/28 amino acids (A / B) | |
| Precursor | (95 aa) | |
| Identifier | ||
| Gene name | HCRT | |
| External IDs | ||
| Occurrence | ||
| Parent taxon | Mammals | |
Orexin A and B (also hypocretin-1 / -2 ) are neuropeptide - hormones in mammals that in the hypothalamus are formed and have an effect on eating behavior and sleep patterns. Further effects are suspected in the autonomic nervous system , in the fluid balance and energy metabolism . They arise through enzymatic cleavage from a precursor protein , the pre-pro-orexin. Mutations in HCRT - gene can narcolepsy also be impaired.
function
Recent research shows that orexin has a strong influence on sleep-wake behavior . For example, narcolepsy is associated with mutations in the gene of the orexin receptor-2 in experimental animal experiments with dogs. In humans, it is assumed that the hypothalamic cell groups (nucleus tuberomamillaris, TMN) are destroyed.
In the lateral hypothalamus and in the zona incerta there are groups of nerve cells that produce orexin and also the melanin-concentrating hormone (MCH). The formation of RNA for both hormones is activated by a transcription factor , the forkhead box protein A2 (Foxa2).
In addition, it was recently shown that the release of orexin is inhibited by leptin , the fat cell's satiety hormone . The metabolism-enhancing (catabolic) function of orexin, namely an increase in body temperature, weight loss, increased alertness and alertness, etc. is becoming increasingly clear.
pharmacology
A team led by Andrew Lawrence from the Howard Florey Institute in Melbourne has found an active ingredient (SB-334867) that blocks the effect of orexins in the brain, which are also said to be responsible for euphoria after drinking alcohol. The research showed that alcohol addiction and eating disorders are based on the same mechanisms, according to study leader Andrew Lawrence.
The orexins develop their effect on the target cells by binding to two different G-protein- coupled receptors, OX 1 R and OX 2 R. Orexin A binds to both receptors in roughly the same way, whereas orexin B mainly binds to OX 2 R.
Names and history
The name orexin (from the Greek ὄρεξις “desire, appetite”) comes from the scientist Masashi Yanagisawa, who found out that an injection of orexin into the hypothalamus increases appetite. (Hence the name hypocretin: The research group led by Luis DeLecea and Tom Kilduff found that orexin in certain key areas (groups of neurons) is produced in the hypothalamus and similarities with other hormones, incretins has, Hypo thalamic In cretin ).
Web links
- Obesity begins in the brain - researchers discover fewer receptors for the messenger substance orexin in sluggish rats
- Why illnesses drain you - Researchers have uncovered the cause of listlessness as a side effect of illnesses
Individual evidence
- ↑ Homologues at OMA
- ↑ UniProt O43612
- ↑ M. Hungs, M. Emmanuel: "Hypocretin / orexin, sleep and narcolepsy" BioEssays (2001) 23: 397-408.
- ^ AJ Lawrence, MS Cowen, HJ Yang, F. Chen, B. Oldfield: The orexin system regulates alcohol-seeking in rats. In: British journal of pharmacology. Volume 148, Number 6, July 2006, pp. 752-759, doi : 10.1038 / sj.bjp.0706789 , PMID 16751790 , PMC 1617074 (free full text).
- ↑ Langmead CJ, Jerman JC, Brough SJ, Scott C, Porter RA, Herdon HJ: Characterization of the binding of [3H] -SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor . In: British Journal of Pharmacology . tape 141 (2) , January 2004, pp. 340-6 ., Doi : 10.1038 / sj.bjp.0705610 , PMID 14691055 , PMC 1574197 (free full text).