Orexin-A
Encyclopedia
Orexin A, also known as Hypocretin-1, is a naturally occurring, highly excitatory, neuropeptide
released by the hypothalamus
. As a pharmaceutical drug, Orexin A is most commonly administered as a nasal spray. This drug counteracts intellectual deficiencies and altered brain
metabolism
, which is found in sleep deprived subjects.
.
tasks. The rhesus monkeys were split into a test group and into a control group. The test group was administered Orexin A intravenously, or nasally. The control group was given a placebo
. The sleep-deprived monkeys, which were given the nasal form of Orexin A, performed far better than the ones treated with injections. Orexin A not only restored the monkey’s cognitive abilities but made their brains appear awake in PET
scans. The same was not true for the control group, which did not exhibit any changes. The findings of these studies strongly favor an effective way to alleviate cognitive limitations due to sleep loss.
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.
, 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 which affected regulating sleep cycles. Tests show a class of potassium ion channels that are porelike proteins in the cell membrane and they 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 absence of glucose inhibited the Orexin neurons by acting on this class of potassium ion channels known as "tandem pore" channels.
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
released by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. As a pharmaceutical drug, Orexin A is most commonly administered as a nasal spray. This drug counteracts intellectual deficiencies and altered brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
, which is found in sleep deprived subjects.
Side effects
To date, taking Orexin A has shown no negative side effects. Positive side effects of this drug include an improvement in cognitive ability and functionality in a sleep deprived state. Taking Orexin A also increases arousal, alertness, attention, and muscle tone. Orexin A has no effect on subjects who are well rested. It is important to note that the study and testing of this drug is fairly new and it has not yet been administered to humans. The most important side effect Orexin A is thought to have is counteracting the effects of narcolepsyNarcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
.
Ongoing research
The subjects of one particular study, rhesus monkeys, were deprived of sleep in durations of 30 to 36 hours, and were immediately assessed in short term memoryMemory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
tasks. The rhesus monkeys were split into a test group and into a control group. The test group was administered Orexin A intravenously, or nasally. The control group was given a placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
. The sleep-deprived monkeys, which were given the nasal form of Orexin A, performed far better than the ones treated with injections. Orexin A not only restored the monkey’s cognitive abilities but made their brains appear awake in PET
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
scans. The same was not true for the control group, which did not exhibit any changes. The findings of these studies strongly favor an effective way to alleviate cognitive limitations due to sleep loss.
Structure
Orexin-A is a peptidePeptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
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.
Mechanism
Orexins are highly excitatory neuropeptide hormones 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 dopamineDopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
and acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
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
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
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
University of Manchester
The University of Manchester is a public research university located in Manchester, United Kingdom. It is a "red brick" university and a member of the Russell Group of research-intensive British universities and the N8 Group...
discovered how glucose inhibited neurons which affected regulating sleep cycles. Tests show a class of potassium ion channels that are porelike proteins in the cell membrane and they 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 absence of glucose inhibited the Orexin neurons by acting on this class of potassium ion channels known as "tandem pore" channels.