Orexin-A

Orexin-A, also known as hypocretin-1, is a naturally occurring neuropeptide and orexin isoform. The orexinergic nucleus in the lateral hypothalamus is the primary orexin projection system in the brain.

Orexin-A is a peptide composed of 33 amino acids including an N-terminal pyroglutamyl residue and two intramolecular disulfide bridges between cysteine residues in 6 and 12 and 7 and 14 positions.

The amino acid sequence is: Pyroglu-Pro-Leu-Pro-Asp-Cys-Cys-Arg-Gln-Lys-Thr-Cys-Ser-Cys-Arg-Leu-Tyr-Glu-Leu-Leu-His-Gly-Ala-Gly-Asn-His-Ala-Ala-Gly-Ile-Leu-Thr-Leu

Orexins are highly excitatory neuropeptides that were first discovered in the brains of rats. It is a peptide that is produced by a very small population of cells in the lateral and posterior hypothalamus. Orexins strongly excite various brain nuclei (neurons) to affect an organism’s wakefulness by affecting their dopamine, norepinephrine, histamine and acetylcholine systems. These systems work together to stabilize the organism’s sleep cycles. Once made, the orexin peptides can bind to the orexin receptor; which is a G protein coupled receptor. This G protein linked receptor senses molecules outside the cell and activates inside signal transduction pathways to elicit cellular responses.

Research shows that an absence of orexin-A appears to cause narcolepsy. Deficit amounts of orexin-A will make people sleepy and research suggests that by adding it back into the brain, narcoleptic effects will be reduced. The research determined how glucose inhibited a particular class of glucose-sensing neurons, which produce tiny proteins called orexins. However, it is unknown how glucose suppresses the electrical activity of orexin cells.

A study from the University of Manchester discovered how glucose inhibited neurons affected the regulation of sleep cycles. Tests show a class of potassium ion channels, pore-like proteins in the cell membrane, affect the cellular responses by controlling the flow of potassium into the cell. The exact mechanism of the potassium ion channels is unknown, but the experiments show that the presence of glucose inhibited the orexin neurons by acting on this class of potassium ion channels known as "tandem pore" channels.

...
Wikipedia