Neuropeptide

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Neuropeptide Y

Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the gut, muscles, and heart.

Contents

There are over 100 known neuropeptides, representing the largest and most diverse class of signaling molecules in the nervous system. Neuropeptides are synthesized from large precursor proteins which are cleaved and post-translationally processed then packaged into dense core vesicles. Neuropeptides are often co-released with other neuropeptides and neurotransmitters in a single neuron, yielding a multitude of effects. Once released, neuropeptides can diffuse widely to affect a broad range of targets.

Synthesis

Neuropeptides are synthesized from large, inactive precursor proteins called prepropeptides. [1] Prepropeptides contain sequences for a family of distinct peptides and often contain repeated copies of the same peptides, depending on the organism. [2] In addition to the precursor peptide sequences, prepropeptides also contain a signal peptide, spacer peptides, and cleavage sites. [3] The signal peptide sequence guides the protein to the secretory pathway, starting at the endoplasmic reticulum. The signal peptide sequence is removed in the endoplasmic reticulum, yielding a propeptide. The propeptide travels to the Golgi apparatus where it is proteolytically cleaved and processed into multiple peptides. Peptides are packaged into dense core vesicles, where further cleaving and processing, such as C-terminal amidation, can occur. Dense core vesicles are transported throughout the neuron and can release peptides at the synaptic cleft, cell body, and along the axon. [1] [4] [5] [6]

Mechanism

Neuropeptides are released by dense core vesicles after depolarization of the cell. Compared to classical neurotransmitter signaling, neuropeptide signaling is more sensitive. Neuropeptide receptor affinity is in the nanomolar to micromolar range while neurotransmitter affinity is in the micromolar to millimolar range. Additionally, dense core vesicles contain a small amount of neuropeptide (3 - 10mM) compared to synaptic vesicles containing neurotransmitters (e.g. 100mM for acetylcholine). [7] Evidence shows that neuropeptides are released after high-frequency firing or bursts, distinguishing dense core vesicle from synaptic vesicle release. [4] Neuropeptides utilize volume transmission and are not reuptaken quickly, allowing diffusion across broad areas (nm to mm) to reach targets. Almost all neuropeptides bind to GPCRs, inducing second messenger cascades to modulate neural activity on long time-scales. [1] [4] [5]

Expression of neuropeptides in the nervous system is diverse. Neuropeptides are often co-released with other neuropeptides and neurotransmitters, yielding a diversity of effects depending on the combination of release. [5] [8] For example, vasoactive intestinal peptide is typically co-released with acetylcholine. [9] Neuropeptide release can also be specific. In Drosophila larvae, for example, eclosion hormone is expressed in just two neurons. [6]

Discovery

The first neuropeptide, Substance P, was discovered by Ulf von Euler and John Gaddum in 1931. [4] [10] In the early 1900s, chemical messengers were crudely extracted from whole animal brains and tissues and studied for their physiological effects. In an effort to isolate and study acetylcholine, von Euler and Gaddum made a crude powder extract from whole equine brain and intestine and found that it induced muscle contractions and depressed blood pressure. The effects were not abolished by atropine and thus could not solely be attributed to acetylcholine. [10] [11] Substance P was first purified and sequenced in 1971 by Michael Chang and Susan Leeman, revealing its 11 amino-acid peptide chain. [11] Similar methods were used to identify other neuropeptides in the early 1950s, such as vasopressin and oxytocin. [12] [13]

In insects, proctolin was the first neuropeptide to be isolated and sequenced. [14] [15] In 1975, Alvin Starratt and Brian Brown extracted the pentapeptide from hindgut muscles of the cockroach and found that its application enhanced muscle contractions. While Starratt and Brown initially thought of proctolin as an excitatory neurotransmitter, proctolin was later confirmed as a neuromodulatory peptide. [16]

The term “neuropeptide” was first used in the 1970s by David de Wied, who studied the effects of the peptide hormones ACTH, MSH, and vasopressin on learning and memory. [17]

Receptor targets

Most neuropeptides act on G-protein coupled receptors (GPCRs). Neuropeptide-GPCRs fall into two families: rhodopsin-like and the secretin class. [18]   Most peptides activate a single GPCR, while some activate multiple GPCRs (e.g. AstA, AstC, DTK). [8] Peptide-GPCR binding relationships are highly conserved across animals. Aside from conserved structural relationships, some peptide-GPCR functions are also conserved across the animal kingdom. For example, neuropeptide F/neuropeptide Y signaling is structurally and functionally conserved between insects and mammals. [8]

Although peptides mostly target metabotropic receptors, there is some evidence that neuropeptides bind to other receptor targets. Peptide-gated ion channels (FMRFamide-gated sodium channels) have been found in snails and Hydra. [19] Other examples of non-GPCR targets include: insulin-like peptides and tyrosine-kinase receptors in Drosophila and atrial natriuretic peptide and eclosion hormone with membrane-bound guanylyl cyclase receptors in mammals and insects. [20]

Actions

Neuropeptides are extremely ancient and highly diverse chemical messengers. Indeed, placozoans such as Trichoplax , extremely basal animals which do not yet possess neurones, use peptides for cell-to-cell communication in a way similar to the neuropeptides of higher animals.

Due to their modulatory and diffusive nature, neuropeptides can act on multiple time and spatial scales. Below are some examples of neuropeptide actions:

Corelease

Neuropeptides are often co-released with other neurotransmitters and neuropeptides to modulate synaptic activity. Synaptic vesicles and dense core vesicles can have differential activation properties for release, resulting in context-dependent corelease combinations. [21] [22] [23] For example, insect motor neurons are glutamatergic and some contain dense core vesicles with proctolin. At low frequency activation, only glutamate is released, yielding fast and rapid excitation of the muscle. At high frequency activation however, dense core vesicles release proctolin, inducing prolonged contractions. [24] Thus, neuropeptide release can be fine-tuned to modulate synaptic activity in certain contexts.

Some regions of the nervous system are specialized to release distinctive sets of peptides. For example, the hypothalamus and the pituitary gland release peptides (e.g. TRH, GnRH, CRH, SST) that act as hormones [25] [26] In one subpoplation of the arcuate nucleus of the hypothalamus, three anorectic peptides are co-expressed: α-melanocyte-stimulating hormone (α-MSH), galanin-like peptide, and cocaine-and-amphetamine-regulated transcript (CART), and in another subpopulation two orexigenic peptides are co-expressed, neuropeptide Y and agouti-related peptide (AGRP). [27] These peptides are all released in different combinations to signal hunger and satiation cues. [28]

The following is a list of neuroactive peptides coreleased with other neurotransmitters. Transmitter names are shown in bold.

Norepinephrine (noradrenaline). In neurons of the A2 cell group in the nucleus of the solitary tract), norepinephrine co-exists with:

GABA

Acetylcholine

Dopamine

Epinephrine (adrenaline)

Serotonin (5-HT)

Some neurons make several different peptides. For instance, vasopressin co-exists with dynorphin and galanin in magnocellular neurons of the supraoptic nucleus and paraventricular nucleus, and with CRF (in parvocellular neurons of the paraventricular nucleus)

Oxytocin in the supraoptic nucleus co-exists with enkephalin, dynorphin, cocaine-and amphetamine regulated transcript (CART) and cholecystokinin.

Evolution of Neuropeptide Signaling

Peptides are ancient signaling systems that are found in almost all animals on Earth (sponges are the exception). [29] [30] Genome sequencing reveals evidence of neuropeptide genes in Cnidaria, Ctenophora, and Placozoa, some of oldest living animals with nervous systems or neural-like tissues. [31] [32] [33] [2] Recent studies also show genomic evidence of neuropeptide processing machinery in metazoans and choanoflagellates, suggesting that neuropeptide signaling may predate the development of nervous tissues. [34] Additionally, Ctenophore and Placozoa neural signaling is entirely peptidergic and lacks the major amine neurotransmitters such as acetylcholine, dopamine, and serotonin. [35] [29] This also suggests that neuropeptide signaling developed before amine neurotransmitters.

Examples

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 and vasopressin have striking and specific effects on social behaviours, including maternal behaviour and pair bonding. CCAP has several functions including regulating heart rate, allatostatin and proctolin regulate food intake and growth, bursicon controls tanning of the cuticle and corazonin has a role in cuticle pigmentation and moulting.

Related Research Articles

<span class="mw-page-title-main">Neurotransmitter</span> Chemical substance that enables neurotransmission

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.

<span class="mw-page-title-main">Acetylcholine</span> Organic chemical and neurotransmitter

Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic.

<span class="mw-page-title-main">Hypothalamus</span> Area of the brain below the thalamus

The hypothalamus is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond.

<span class="mw-page-title-main">Oxytocin</span> Peptide hormone and neuropeptide

Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin is released into the bloodstream as a hormone in response to sexual activity and during labour. It is also available in pharmaceutical form. In either form, oxytocin stimulates uterine contractions to speed up the process of childbirth. In its natural form, it also plays a role in maternal bonding and milk production. Production and secretion of oxytocin is controlled by a positive feedback mechanism, where its initial release stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases. A similar process takes place during lactation and during sexual activity.

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.

<span class="mw-page-title-main">Supraoptic nucleus</span> ADH secreting nucleus of the hypothalamus.

The supraoptic nucleus (SON) 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. In humans, the SON contains about 3,000 neurons.

<span class="mw-page-title-main">Paraventricular nucleus of hypothalamus</span>

The paraventricular nucleus is a nucleus in the hypothalamus. Anatomically, it is adjacent to the third ventricle and many of its neurons project to the posterior pituitary. These projecting neurons secrete oxytocin and a smaller amount of vasopressin, otherwise the nucleus also secretes corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). CRH and TRH are secreted into the hypophyseal portal system and act on different targets neurons in the anterior pituitary. PVN is thought to mediate many diverse functions through these different hormones, including osmoregulation, appetite, and the response of the body to stress.

Magnocellular neurosecretory cells are large neuroendocrine cells within the supraoptic nucleus and paraventricular nucleus of the hypothalamus. They are also found in smaller numbers in accessory cell groups between these two nuclei, the largest one being the circular nucleus. There are two types of magnocellular neurosecretory cells, oxytocin-producing cells and vasopressin-producing cells, but a small number can produce both hormones. These cells are neuroendocrine neurons, are electrically excitable, and generate action potentials in response to afferent stimulation. Vasopressin is produced from the vasopressin-producing cells via the AVP gene, a molecular output of circadian pathways.

<span class="mw-page-title-main">Arcuate nucleus</span>

The arcuate nucleus of the hypothalamus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.

<span class="mw-page-title-main">End-plate potential</span>

End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters are exocytosed and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.4mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine-containing vesicle. It represents the smallest possible depolarization which can be induced in a muscle.

Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.

β-Endorphin Peptide hormone in humans

β-Endorphin (beta-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in humans, the others of which include α-endorphin and γ-endorphin.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

An autoreceptor is a type of receptor located in the membranes of nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the autoreceptor sits. Similarly, a heteroreceptor is sensitive to neurotransmitters and hormones that are not released by the cell on which it sits. A given receptor can act as either an autoreceptor or a heteroreceptor, depending upon the type of transmitter released by the cell on which it is embedded.

Neuroendocrinology is the branch of biology which studies the interaction between the nervous system and the endocrine system; i.e. how the brain regulates the hormonal activity in the body. The nervous and endocrine systems often act together in a process called neuroendocrine integration, to regulate the physiological processes of the human body. Neuroendocrinology arose from the recognition that the brain, especially the hypothalamus, controls secretion of pituitary gland hormones, and has subsequently expanded to investigate numerous interconnections of the endocrine and nervous systems.

<span class="mw-page-title-main">Neurotransmission</span> Impulse transmission between neurons

Neurotransmission is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron, and bind to and react with the receptors on the dendrites of another neuron a short distance away. A similar process occurs in retrograde neurotransmission, where the dendrites of the postsynaptic neuron release retrograde neurotransmitters that signal through receptors that are located on the axon terminal of the presynaptic neuron, mainly at GABAergic and glutamatergic synapses.

In biology, cell signaling is the process by which a cell interacts with itself, other cells and the environment. Cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes.

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfigurating synaptic connectivity.

<span class="mw-page-title-main">Synapse</span> Structure connecting neurons in the nervous system

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another neuron or to the target effector cell.

<span class="mw-page-title-main">Galanin</span>

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.

References

  1. 1 2 3 Mains RE, Eipper BA (1999). "The Neuropeptides". Basic Neurochemistry (6th ed.). Lippincott-Raven. ISBN   978-0-397-51820-3.
  2. 1 2 Elphick MR, Mirabeau O, Larhammar D (February 2018). "Evolution of neuropeptide signalling systems". The Journal of Experimental Biology. 221 (Pt 3): jeb151092. doi:10.1242/jeb.151092. PMC   5818035 . PMID   29440283.
  3. ↑ "nEUROSTRESSPEP: Insect Neuropeptides". www.neurostresspep.eu. Retrieved 25 August 2021.
  4. 1 2 3 4 Hökfelt T, Bartfai T, Bloom F (August 2003). "Neuropeptides: opportunities for drug discovery". The Lancet. Neurology. 2 (8): 463–472. doi:10.1016/S1474-4422(03)00482-4. PMID   12878434. S2CID   23326450.
  5. 1 2 3 Russo AF (May 2017). "Overview of Neuropeptides: Awakening the Senses?". Headache. 57 (Suppl 2): 37–46. doi:10.1111/head.13084. PMC   5424629 . PMID   28485842.
  6. 1 2 Nässel DR, Zandawala M (August 2019). "Recent advances in neuropeptide signaling in Drosophila, from genes to physiology and behavior". Progress in Neurobiology. 179: 101607. doi:10.1016/j.pneurobio.2019.02.003. PMID   30905728. S2CID   84846652.
  7. ↑ Mains RE, Eipper BA (1999). "The Neuropeptides". Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Lippincott-Raven.
  8. 1 2 3 Nässel DR, Winther AM (September 2010). "Drosophila neuropeptides in regulation of physiology and behavior". Progress in Neurobiology. 92 (1): 42–104. doi:10.1016/j.pneurobio.2010.04.010. PMID   20447440. S2CID   24350305.
  9. ↑ Dori I, Parnavelas JG (July 1989). "The cholinergic innervation of the rat cerebral cortex shows two distinct phases in development". Experimental Brain Research. 76 (2): 417–423. doi:10.1007/BF00247899. PMID   2767193. S2CID   19504097.
  10. 1 2 V Euler US, Gaddum JH (June 1931). "An unidentified depressor substance in certain tissue extracts". The Journal of Physiology. 72 (1): 74–87. doi:10.1113/jphysiol.1931.sp002763. PMC   1403098 . PMID   16994201.
  11. 1 2 Chang MM, Leeman SE, Niall HD (July 1971). "Amino-acid sequence of substance P". Nature. 232 (29): 86–87. doi:10.1038/newbio232086a0. PMID   5285346.
  12. ↑ Du Vigneaud V, Ressler C, Trippett S (December 1953). "The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin". The Journal of Biological Chemistry. 205 (2): 949–957. doi: 10.1016/S0021-9258(18)49238-1 . PMID   13129273.
  13. ↑ Turner RA, Pierce JG, du VIGNEAUD V (July 1951). "The purification and the amino acid content of vasopressin preparations". The Journal of Biological Chemistry. 191 (1): 21–28. doi: 10.1016/S0021-9258(18)50947-9 . PMID   14850440.
  14. ↑ Lange AB, Orchard I (2006). "Proctolin in Insects". Handbook of Biologically Active Peptides. pp. 177–181. doi:10.1016/B978-012369442-3/50030-1. ISBN   9780123694423.
  15. ↑ Starratt AN, Brown BE (October 1975). "Structure of the pentapeptide proctolin, a proposed neurotransmitter in insects". Life Sciences. 17 (8): 1253–1256. doi:10.1016/0024-3205(75)90134-4. PMID   576.
  16. ↑ Tanaka Y (2016). "Proctolin". Handbook of Hormones. doi:10.1016/B978-0-12-801028-0.00067-2. ISBN   9780128010280.
  17. ↑ Burbach JP (2011). "What Are Neuropeptides?". Neuropeptides. Methods in Molecular Biology. Vol. 789. pp. 1–36. doi:10.1007/978-1-61779-310-3_1. ISBN   978-1-61779-309-7. PMID   21922398.
  18. ↑ Brody T, Cravchik A (July 2000). "Drosophila melanogaster G protein-coupled receptors". The Journal of Cell Biology. 150 (2): F83–F88. doi:10.1083/jcb.150.2.f83. PMC   2180217 . PMID   10908591.
  19. ↑ Dürrnagel S, Kuhn A, Tsiairis CD, Williamson M, Kalbacher H, Grimmelikhuijzen CJ, et al. (April 2010). "Three homologous subunits form a high affinity peptide-gated ion channel in Hydra". The Journal of Biological Chemistry. 285 (16): 11958–11965. doi: 10.1074/jbc.M109.059998 . PMC   2852933 . PMID   20159980.
  20. ↑ Chang JC, Yang RB, Adams ME, Lu KH (August 2009). "Receptor guanylyl cyclases in Inka cells targeted by eclosion hormone". Proceedings of the National Academy of Sciences of the United States of America. 106 (32): 13371–13376. Bibcode:2009PNAS..10613371C. doi: 10.1073/pnas.0812593106 . PMC   2726410 . PMID   19666575.
  21. ↑ Nässel DR (23 March 2018). "Substrates for Neuronal Cotransmission With Neuropeptides and Small Molecule Neurotransmitters in Drosophila". Frontiers in Cellular Neuroscience. 12: 83. doi: 10.3389/fncel.2018.00083 . PMC   5885757 . PMID   29651236.
  22. ↑ van den Pol AN (October 2012). "Neuropeptide transmission in brain circuits". Neuron. 76 (1): 98–115. doi:10.1016/j.neuron.2012.09.014. PMC   3918222 . PMID   23040809.
  23. ↑ Nusbaum MP, Blitz DM, Swensen AM, Wood D, Marder E (March 2001). "The roles of co-transmission in neural network modulation". Trends in Neurosciences. 24 (3): 146–154. doi:10.1016/S0166-2236(00)01723-9. PMID   11182454. S2CID   8994646.
  24. ↑ Adams ME, O'Shea M (July 1983). "Peptide cotransmitter at a neuromuscular junction". Science. 221 (4607): 286–289. Bibcode:1983Sci...221..286A. doi:10.1126/science.6134339. PMID   6134339.
  25. ↑ "The Nobel Prize in Physiology or Medicine 1977". NobelPrize.org. Retrieved 15 December 2021.
  26. ↑ Childs GV, Westlund KN, Tibolt RE, Lloyd JM (September 1991). "Hypothalamic regulatory peptides and their receptors: cytochemical studies of their role in regulation at the adenohypophyseal level". Journal of Electron Microscopy Technique. 19 (1): 21–41. doi:10.1002/jemt.1060190104. PMID   1660066.
  27. ↑ Lau J, Farzi A, Qi Y, Heilbronn R, Mietzsch M, Shi YC, Herzog H (January 2018). "CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis". Molecular Metabolism. 7: 102–118. doi:10.1016/j.molmet.2017.10.015. PMC   5784325 . PMID   29146410.
  28. ↑ Luckman SM, Lawrence CB (March 2003). "Anorectic brainstem peptides: more pieces to the puzzle". Trends in Endocrinology and Metabolism. 14 (2): 60–65. doi:10.1016/S1043-2760(02)00033-4. PMID   12591175. S2CID   25055675.
  29. 1 2 Schoofs L, De Loof A, Van Hiel MB (January 2017). "Neuropeptides as Regulators of Behavior in Insects". Annual Review of Entomology. 62: 35–52. doi: 10.1146/annurev-ento-031616-035500 . PMID   27813667.
  30. ↑ Jékely G (March 2021). "The chemical brain hypothesis for the origin of nervous systems". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 376 (1821): 20190761. doi:10.1098/rstb.2019.0761. PMC   7935135 . PMID   33550946.
  31. ↑ Sachkova MY, Nordmann EL, Soto-Àngel JJ, Meeda Y, Górski B, Naumann B, et al. (December 2021). "Neuropeptide repertoire and 3D anatomy of the ctenophore nervous system". Current Biology. 31 (23): 5274–5285.e6. doi: 10.1016/j.cub.2021.09.005 . PMID   34587474. S2CID   238210404.
  32. ↑ Takahashi T, Takeda N (January 2015). "Insight into the molecular and functional diversity of cnidarian neuropeptides". International Journal of Molecular Sciences. 16 (2): 2610–2625. doi: 10.3390/ijms16022610 . PMC   4346854 . PMID   25625515.
  33. ↑ Mirabeau O, Joly JS (May 2013). "Molecular evolution of peptidergic signaling systems in bilaterians". Proceedings of the National Academy of Sciences of the United States of America. 110 (22): E2028–E2037. Bibcode:2013PNAS..110E2028M. doi: 10.1073/pnas.1219956110 . PMC   3670399 . PMID   23671109.
  34. ↑ Yañez-Guerra LA, Thiel D, Jékely G (April 2022). "Premetazoan Origin of Neuropeptide Signaling". Molecular Biology and Evolution. 39 (4): msac051. doi:10.1093/molbev/msac051. PMC   9004410 . PMID   35277960.
  35. ↑ Varoqueaux F, Williams EA, Grandemange S, Truscello L, Kamm K, Schierwater B, et al. (November 2018). "High Cell Diversity and Complex Peptidergic Signaling Underlie Placozoan Behavior". Current Biology. 28 (21): 3495–3501.e2. doi: 10.1016/j.cub.2018.08.067 . PMID   30344118. S2CID   53044824.
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