Neuropeptide
Encyclopedia
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s to communicate with each other. They are neuronal signaling molecules, influence the activity of the 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,...
in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and memory.
Neuropeptides are expressed and released by neurons, and mediate or modulate neuronal communication by acting on cell surface receptors. The human genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
contains about 90 genes that encode precursors of neuropeptides. At present about 100 different peptides are known to be released by different populations of neurons in the mammalian brain. Neurons use many different chemical signals to communicate information, including neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s, peptides, cannabinoids, and even some gases, like nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
.
Many populations of neurons have distinctive biochemical phenotypes. For example, in one subpopulation of about 3000 neurons in the arcuate nucleus
Arcuate nucleus
The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence...
of the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, three anorectic
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
peptides are co-expressed: α-melanocyte-stimulating hormone (α-MSH), galanin-like peptide
Galanin-like peptide
Galanin-like peptide is a neuropeptide present in humans and other mammals. It is a 60-amino acid polypeptide produced in the arcuate nucleus of the hypothalamus and the posterior pituitary gland. It is involved in the regulation of appetite and may also have other roles such as in inflammation,...
, and cocaine-and-amphetamine-regulated transcript (CART), and in another subpopulation two orexigenic peptides are co-expressed, neuropeptide Y
Neuropeptide Y
Neuropeptide Y is a 36-amino acid peptide neurotransmitter found in the brain and autonomic nervous system."NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy." The main effect is increased food...
and agouti-related peptide
Agouti-related peptide
Agouti-related protein also called Agouti-related peptide is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is only synthesised in NPY containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus...
(AGRP). These are not the only peptides in the arcuate nucleus; β-endorphin, dynorphin
Dynorphin
Dynorphins are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 , multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neo-endorphin...
, enkephalin
Enkephalin
An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin were revealed, one...
, galanin
Galanin
Galanin is a neuropeptide encoded by the GAL gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors....
, ghrelin
Ghrelin
Ghrelin is a 28 amino acid peptide and hormone that is produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone...
, growth-hormone releasing hormone, neurotensin
Neurotensin
Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system...
, neuromedin U
Neuromedin U
Neuromedin U is a neuropeptide found in the brain of humans and other mammals, which has a number of diverse functions including contraction of smooth muscle, regulation of blood pressure, pain perception, appetite, bone growth, and hormone release...
, and somatostatin
Somatostatin
Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
are also expressed in subpopulations of arcuate neurons. These peptides are all released centrally and act on other neurons at specific receptors. The neuropeptide Y neurons also make the classical inhibitory neurotransmitter GABA
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
.
Invertebrates also have many neuropeptides. CCAP
Crustacean Cardioactive Peptide
Crustacean cardioactive peptide is a highly conserved, amidated cyclic nonapeptide with the primary structure PFCNAFTGC-NH2 and a disulfide bridge between Cys3 and Cys9. It is found in crustaceans and insects where it behaves as a cardioaccelerator, neuropeptide transmitter for other areas of the...
has several functions including regulating heart rate, allatostatin
Allatostatin
Allatostatins are neuropeptide hormones in insects and crustacea. They have a twofold function: they both inhibit the generation of juvenile hormone and reduce their food intake. They are therefore putative targets for insecticide research....
and proctolin
Proctolin
Proctolin is a neuropeptide present in insects and crustaceans. It was first found in Periplaneta americana, a species of cockroach in 1975. Proctolin was extracted from 125,000 cockroaches and the Edman degradation was carried out on the sample to determine the amino acid sequence, which is...
regulate food intake and growth, bursicon
Bursicon
Bursicon is an insect hormone which mediates tanning in the cuticle of adult flies.-Structure:...
controls tanning of the cuticle and corazonin
Corazonin
Corazonin is a highly conserved neuropeptide found in many insects, in particular locusts and cockroaches.- Structure :Corazonin is an undecapeptide with the amino acid sequence Glu-Thr-Phe-Gln-Tyr-Ser-Arg-Gly-Trp-Thr-Asn-amide. It is blocked by pGlu at its N-terminal side and amidated at its...
has a role in cuticle pigmentation and moulting.
Peptide signals play a role in information processing that is different from that of conventional neurotransmitters, and many appear to be particularly associated with specific behaviours. For example, oxytocin
Oxytocin
Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
and vasopressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
have striking and specific effects on social behaviours, including maternal behaviour and pair bonding.
Function
Generally, peptides act at metabotropic or G-protein-coupled receptors expressed by selective populations of neurons. In essence they act as specific signals between one population of neurons and another. Neurotransmitters generally affect the excitability of other neurons, by depolarising them or by hyperpolarising them. Peptides have much more diverse effects; amongst other things, they can affect gene expression, local blood flow, synaptogenesisSynaptogenesis
Synaptogenesis is the formation of synapses. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development...
, and glial cell morphology. Peptides tend to have prolonged actions, and some have striking effects on behaviour.
Neurons very often make both a conventional neurotransmitter (such as glutamate
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
, GABA
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
or dopamine
Dopamine
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...
) and one or more neuropeptides. Peptides are generally packaged in large dense-core vesicles, and the co-existing neurotransmitters in small synaptic vesicles. The large dense-core vesicles are often found in all parts of a neuron, including the soma
Soma
Soma , or Haoma , from Proto-Indo-Iranian *sauma-, was a ritual drink of importance among the early Indo-Iranians, and the subsequent Vedic and greater Persian cultures. It is frequently mentioned in the Rigveda, whose Soma Mandala contains 114 hymns, many praising its energizing qualities...
, dendrites, axonal swellings (vericosities) and nerve endings, whereas the small synaptic vesicles are mainly found in clusters at presynaptic locations. Release of the large vesicles and the small vesicles is regulated differentially.
Examples
The following is a list of neuroactive peptides coexisting with other neurotransmitters. Transmitter names are shown in bold.Norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline).
In neurons of the A2 cell group in the nucleus of the solitary tract), norepinephrine co-exists with:
- GalaninGalaninGalanin is a neuropeptide encoded by the GAL gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors....
- EnkephalinEnkephalinAn enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin were revealed, one...
- Neuropeptide YNeuropeptide YNeuropeptide Y is a 36-amino acid peptide neurotransmitter found in the brain and autonomic nervous system."NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy." The main effect is increased food...
GABA
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
- SomatostatinSomatostatinSomatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
(in the hippocampusHippocampusThe hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
) - CholecystokininCholecystokininCholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...
- Neuropeptide YNeuropeptide YNeuropeptide Y is a 36-amino acid peptide neurotransmitter found in the brain and autonomic nervous system."NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy." The main effect is increased food...
(in the arcuate nucleusArcuate nucleusThe arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence...
)
Acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
- VIPVasoactive intestinal peptideVasoactive intestinal peptide also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 29 amino acid residues that is produced in many tissues of vertebrates including the gut, pancreas and suprachiasmatic nuclei of the hypothalamus in the brain...
- Substance PSubstance PIn the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
Dopamine
Dopamine
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...
- CholecystokininCholecystokininCholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...
- NeurotensinNeurotensinNeurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system...
Epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(adrenaline)
- Neuropeptide YNeuropeptide YNeuropeptide Y is a 36-amino acid peptide neurotransmitter found in the brain and autonomic nervous system."NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy." The main effect is increased food...
- NeurotensinNeurotensinNeurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system...
Serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
(5-HT)
- Substance PSubstance PIn the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
- TRH
- EnkephalinEnkephalinAn enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin were revealed, one...
Some neurons make several different peptides. For instance,
Vasopressin
Vasopressin
Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
co-exists with dynorphin
Dynorphin
Dynorphins are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 , multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neo-endorphin...
and galanin
Galanin
Galanin is a neuropeptide encoded by the GAL gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors....
in magnocellular neurons of the supraoptic nucleus
Supraoptic nucleus
The supraoptic nucleus is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm...
and paraventricular nucleus
Paraventricular nucleus
The paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
, and with CRF
CRF
CRF may refer to:Science and technology* Corticotropin-releasing factor, also called corticotropin-releasing hormone and corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
(in parvocellular neurons of the paraventricular nucleus
Paraventricular nucleus
The paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
)
Oxytocin
Oxytocin
Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
in the supraoptic nucleus
Supraoptic nucleus
The supraoptic nucleus is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm...
co-exists with enkephalin
Enkephalin
An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin were revealed, one...
, dynorphin
Dynorphin
Dynorphins are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 , multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neo-endorphin...
, cocaine-and amphetamine regulated transcript (CART) and cholecystokinin
Cholecystokinin
Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...
.
Diabetes link
A 2006 discovery might have important implications for treatment of diabetes,. Researchers at the Toronto Hospital for Sick ChildrenHospital for Sick Children
The Hospital for Sick Children – is a major paediatric centre for the Greater Toronto Area, serving patients up to age 18. Located on University Avenue in Downtown Toronto, SickKids is part of the city’s Discovery District, a critical mass of scientists and entrepreneurs who are focused on...
injected capsaicin
Capsaicin
Capsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...
into NOD mice
NOD mice
Non-obese diabetic or NOD mice, like the Biobreeding rat, are used as an animal model for type 1 diabetes.- History :Non-obese diabetic mice exhibit a susceptibility to spontaneous development of autoimmune insulin dependent diabetes mellitus...
(Non-obese diabetic mice, a strain that is genetically predisposed to develop the equivalent of Type 1 diabetes) to kill the pancreatic sensory nerves
Sensory nerves
Sensory nerves are nerves that receive sensory stimuli, such as how something feels and if it is painful, smooth, rough, etc.They are made up of nerve fibers, called sensory fibers .Sensory neurons are neurons that are activated by sensory input Sensory nerves are nerves that receive sensory...
. This treatment reduced the development of diabetes in these mice by 80%, suggesting a link between neuropeptides and the development of Type 1 diabetes. When the researchers injected the pancreas of the diabetic mice with substance P, they were cured of the diabetes for as long as 4 months. Also, insulin resistance (characteristic of type 2 diabetes) was reduced. These research results are in the process of being confirmed, and their applicability in humans will have to be established in the future. Any treatment that could result from this research is probably years away.
Depression Link
There are studies investigating the relation of neuropeptides and CNS disorders including depression.External links
See also
- Candace PertCandace PertCandace Beebe Pert is an American neuroscientist and pharmacologist who discovered the opiate receptor, the cellular binding site for endorphins in the brain.-History:...