Neurokinin B

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Neurokinin B
Neurokinin B.png
Identifiers
86933-75-7 YesY
ChemSpider 4470819 N
Jmol-3D images Image
MeSH Neurokinin+B
PubChem 55583
Properties
C55H79N13O14S2
Molar mass 1210.43
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N verify (what isYesY/N?)
Infobox references

Neurokinin B,NKB, belongs in the family of Tachykinin peptides. Neurokinin B is implicated in a variety of human functions and pathways such as those of Gonadotropin-releasing hormone secretion [1] Additionally, NKB, is associated with pregnancy in females and maturation in young adults. Reproductive function is highly dependent on levels of not only Neurokinin B but also Kisspeptin.[2] The first instances of study done to learn more about NKB came after it was found that high levels of the peptide may be implicated in a condition known as Pre-eclampsia during pregnancy.[3] Neurokinin B along with Kisspeptin and Dynorphin together are found in the Arcuate Nucleus (ARC) known as the KNDy subpopulation. These cells are targeted by a large number of steroid hormones and work together to form a network that feeds back to GnRH pulse generator [4]

Synthesis[edit]

Neurokinin b is found in humans as a ten-peptide chain (decapeptide) attached to an end of chain amide group. The peptide formula is as follows, H-Asp-Met-His-Asp-Phe-Phe-Val-Gly-Leu-Met-NH2.[5] Neurokinin b (NKB), is encoded by the TAC3 gene in humans and Tac2 in rodent species.[6] Neurokinin b is expressed along with the peptides Kisspeptin and dynorphin A in the neuronal cells of the arcuate nucleus.[6] Five exon segments in the TAC3 gene encode for the NKB precursor known as preprotachykinin B. Preprotachykinin B is in a later step proteolytically cleaved into the pro-peptide, proneurokinin B. Following another cleavage from proneurokinin B, the final product, Neurokinin B is produced.[6]

NKB in Humans[edit]

During the Ovarian cycle GnRH secretion along with that of leutenizing hormone (LH) is highly regulated by a negative feedback system in with Neurokinin b along with its sister peptides the KNDy cell bodies play a role in. The NK3R receptor group when activated with a synthetic agonist of NKB, senktide, has been shown to stimuulate the secretion of leutenizing hormone.[4] In addition, it seems NKB plays a larger role in females than in males. It has been found that in brain of females, the arcuate nucleus contains twice as many connections to NKB neurons than males.[1]

Receptors[edit]

The main receptor Neurokinin B interacts with is the neurokinin 3 receptor (NK3R).[6] The Neurokinin 3 receptor is a part of a larger family of G-protein coupled receptors in which all tachykinin proteins bind. While Neurokinin B has the ability to bind to other Neurokinin receptors, the highest affinity lies in that of the NK3R receptor group.[6] Much like the Neurokinin B peptide the NK3R receptor it binds to is encoded within five exons of the TACR3 gene in humans and the Tacr3 gene in mice and other rodents.[6] High concentrations of the NK3R receptor are found in both the Central Nervous System and the spinal cord. Additional NK3R receptors have also been found in various other places in the body including: uterus, mesenteric vein, gut neurons, and placenta.[6] In addition, Neurokinin b has also been found to co-localize certain gonadal steroid hormone receptors. These include the estrogen receptor (ERα), Progesterone receptor (PR) and androgen receptor. It has been found that co-localization of the NKB neurons near these receptors is at a much higher concentration than even that of other peptides and chemicals. The Kisspeptin, Neurokinin b, and Dynorphin cell groups are found to be co-localized to more than 95% of all of the aforementioned receptors in the arcuate nucleus.[4]

Role in release of Gonadotropin-Releasing Hormone[edit]

Mutations or defects in the TAC3 or TAC3R gene can lead to steroidal feedback problems in the GnRH pulse generator loop causing GnRH to be understimulated leading to hypogonadism.[4] During a review of neurokinin b along with its sister peptides, kisspeptin and dynorphin, it was found in sheep that that these KNDy cell groups (Kisspeptin, Neurokinin b, Dynorphin), are in direct contact with the GnRH neuronal bodies in both the pre optic Area and the mediobasal hypothalamus. Researchers found this to be consistent among species including humans.[4] Due to the high percentage of co-localization found with Neurokinin b cell bodies and receptor groups it is suggested that Neurokinin b along with kisspeptin and dynorphin play a role in the release of GnRH.[4] These findings are important since GnRH release plays such a huge role in regulating hormonal control in the bodies of humans.

References[edit]

  1. ^ a b Goodman, R.L; Coolen, L.M; Lehman, M.N (July 2014). "A Role for Neurokinin B in Pulsatile GnRH Secretion in the Ewe". Neuro-endocinology 99 (1). doi:10.1159/000355285. 
  2. ^ Navarro, VM (2013). "Interactions between kisspeptins and neurokinin B". Adv Exp Med Biol 784: 325–347. doi:10.1007/978-1-4614-6199-9_15. Retrieved 9 March 2015. 
  3. ^ Rie, Sakamoto; hisao, Osada; Yoshinori, Litsuka; Kentarou, Masuda; Kenshi, Kaku; Katsuyoshi, Seki; Souei, Sekiya (17 Apr 2003). "Profile of neurokinin B concentrations in maternal and cord blood in normal pregnancy". Clinical Endocrinology 58 (5): 597–600. 
  4. ^ a b c d e f Lehman, Michael; Coolen, Lique; Goodman, Robert (August 2010). "Minireview: Kisspeptin/Neurokinin B/ Dynorphin Cells of the Arcuate Nucleus: A central Node in the Control of Gonadotorpin-Releasing Hormone Secretion". Endocrinology 151 (8). doi:10.1210/en.2010-0022. Retrieved 19 March 2015. 
  5. ^ Hasimoto, Tadashi; Uchida, Yoshiki; Okimura, Keiko; Kurosawa, Katsuro (1986). "Synthesis of Neurokinin B analogs and Their Activities as Agonists and Antagonists". Chem.Pharm. 
  6. ^ a b c d e f g Navarro, VM (2013). "Interactions between kisspeptins and neurokinin B". Adv Exp Med Biol 784: 325–347. doi:10.1007/978-1-4614-6119-9_15.