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).
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