The Introduction of Orexin A

2018-10-09

Introduction 

Orexin A (OXA) and orexin B (OXB) are hypothalamic neuropeptides discovered in 1998, which bind to two G-protein coupled receptors (GPCRs), namely orexin receptor 1 (OX1) and orexin receptor 2 (OX2). Among them, OX1 was first discovered with a higher affinity to OXA. A considerable amount of data show that OXA and receptors are involved in the regulation of various physiological functions, including feeding, sleep/wake cycle, growth, reproduction, stress, energy homeostasis, and endocrine. Recent studies have shown that the orexin system is also involved in the regulation of cell proliferation and apoptosis. In addition to the central nervous system, peripheral tissues also have expression of the orexin system. In 1999, some scholars found that OXA and OX1 were expressed in rat pancreatic tissue, indicating that OXA and its receptor OX1 are involved in the regulation of islet cell function. Several experiments have confirmed that OXA can affect insulin secretion in vivo and in vitro, but the conclusions are not consistent, and the mechanism is still unclear.

Function

The orexin system plays an important role in energy balance, wake/sleep cycle, metabolism, regulation of non-sleep energy consumption, and reward processing. Therefore, these receptors are considered to be potential targets for the treatment of numerous diseases such as insomnia, lethargy, obesity and drug addiction. OXA (17-33) is highly selective for OX1 (∼23-fold) and is currently the shortest analogue for OX1 selectivity. OXA (17-33) has 9-fold reduction in activity at OX2 and 700-fold lower than OX1. These results indicate that the effect of strand orientation on the orexin receptor binding in this region is more pronounced.

Application

Given its short sequence and high selectivity toward OX1, OXA (17-33) may serve as an improved biological probe of the OX1 receptor function. During single amino acid mutagenesis, OXA (17-33) seems to maintain structural requirements similar to those reported for orexin A and OXA (15-33).

References:

de Lecea, L.; Kilduff, T. S.; Peyron, C.; Gao, X.; Foye, P. E.; Danielson, P. E.; Fukuhara, C.; Battenberg, E. L.; Gautvik, V. T.; Bartlett, F. S., II; Frankel, W. N.; van den Pol, A. N.; Bloom, F. E.; Gautvik, K. M.; Sutcliffe, J. G. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 322-327.

Sakurai, T.; Amemiya, A.; Ishii, M.; Matsuzaki, I.; Chemelli, R. M.; Tanaka, H.; Williams, S. C.; Richardson, J. A.; Kozlowski, G. P.; Wilson, S.; Arch, J. R.; Buckingham, R. E.; Haynes, A. C.; Carr, S. A.; Annan, R. S.; McNulty, D. E.; Liu, W. S.; Terrett, J. A.; Elshourbagy, N. A.; Bergsma, D. J.; Yanagisawa, M. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998, 92, 573-585.

Sakurai, T. Roles of orexins and orexin receptors in central regulation of feeding behavior and energy homeostasis. CNS Neurol. Disord.: Drug Targets 2006, 5, 313-325.

Chemelli, R. M.; Willie, J. T.; Sinton, C. M.; Elmquist, J. K.; Scammell, T.; Lee, C.; Richardson, J. A.; Williams, S. C.; Xiong, Y.; Kisanuki, Y.; Fitch, T. E.; Nakazato, M.; Hammer, R. E.; Saper, C. B.; Yanagisawa, M. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999, 98, 437-451.

Lubkin, M.; Stricker-Krongrad, A. Independent feeding and metabolic actions of orexins in mice. Biochem. Biophys. Res. Commun. 1998, 253, 241-245.

Creative Peptides has accumulated a huge library of peptide knowledge including frontier peptide articles, application of peptides, useful tools, and more!

ICl 154,129 is a new compound that shows selectivity as an antagonist of [Leu5]enkephalin and [D-AIa2, D-Leu5]en ...

An of Dipeptide A Peptide is a constituent fragment in the structure of a protein and is linked by an amide bond ...

 PBP 10 (RhoB-Glu-Arg-Leu-Phe-Glc-Val-Lys-Glc-Arg-Arg) is a 10-aa-long rhodamine-linked and membrane-permeable pe ...

  Perindopril erbumine is an angiotensioncon vertingenzyme (ACE) inhibitor without sulfhydryl group. It is a chi ...

 Appropriate perfusion preservation solution is of great significance for reducing or slowing down various damage ...

Contact Us

USA

Address:

Tel: |

Email:

Germany

Address:

Copyright © 2024 Creative Peptides. All rights reserved.