86933-75-7 Usage
Description
Neurokinin B (NKB) is a peptide hormone that belongs to the tachykinin family and is encoded by the TAC3 gene in vertebrates. It was first isolated from the porcine spinal cord in 1983 and has since been characterized in various tetrapod species. NKB plays a crucial role in the regulation of various physiological processes, including stress response, pain transmission, and reproductive functions.
Uses
Used in Pharmaceutical Industry:
Neurokinin B is used as a target for the development of drugs that modulate the activity of the neurokinin-3 receptor (NK3R). Agonists and antagonists of NK3R, such as senktide, [MePhe7]NKB, osanetant, and talnetant, have been developed and are commercially available. These drugs have potential therapeutic applications in the treatment of various disorders, including stress-related conditions, chronic pain, and endometriosis.
Used in Research:
Neurokinin B is used as a research tool to study the physiological roles and mechanisms of action of the tachykinin family of peptides and their receptors. It helps researchers to understand the complex interactions between the nervous, endocrine, and immune systems, as well as the role of NKB in the regulation of stress response, pain transmission, and reproductive functions.
It should be noted that there is limited evidence for the pharmacological activity of mammalian NK3 agonists or antagonists on nonvertebrate homologs, indicating the need for further research in this area.
Structure
Tetrapod NKBs are composed of 10 amino acids. In several teleosts such as the zebrafish and salmon,NKBa consists
of 10 amino acids, whereas NKBb, another zebrafish NKB
subtype, has 24 amino acids. NKF is composed of 13 aa.
All tac3-derived peptides share the C-terminal Phe-X-Gly-Leu-Met-amide tachykinin (TK) sequence.In particular,
NKBs and NKFs almost exclusively contain Val at the “X”
position, as seeninNKA family peptides. Comparedwith
NKA, NKB possesses no basic amino acid (Lys or Arg).
These motifs and residues have been shown to play crucial
roles in receptor activation and binding selectivity.
Gene, mRNA, and precursor
NKB is encoded in tac3 (or pptB). Vertebrate tac3 is organized by seven or eight exons. Most tetrapod NKB is
present as a single copy in the fifth exon. To date, several
splicing variants have been shown to be generated from
tac3 in mammals while only NKB is produced from these
precursors. In several teleosts including zebrafish and
salmon, two tac3, tac3a and tac3b, are present. For instance,
zebrafish tac3a encodes one 10-amino acid NKBa and one
NKF, whereas one 24-aa NKBb and one additional NKF
are encoded by tac3b, where only the second Asn of
tac3a-derived NKF is replaced with Asp.
Receptors
TK receptors, namely NK1 (TACR1), NK2 (TACR2),
and NK3 (TACR3), belong to the class A G protein-coupled receptor family. NKB displays selective affinity to NK3. In most teleosts, two subtypes, namely
tac3ra and tac3rb, are conserved. NKF activated human
NK3, and zebrafish TACR3a and TACR3b comparable to
mammalian NKB or zebrafish NKBa, whereas zebrafish
NKBb is 100- to 100-fold less potent than these NKB family peptides.
Signal transduction pathway
Mammalian and zebrafish NK3, expressed in Xenopus
oocytes or cultured cells, triggers intracellular calcium
mobilization and cAMP production in response to their
selective ligands, followed by the activation of PKC,
MAPK, and ERK phosphorylation in a cell- or tissuespecific manner.
Biological functions
In mammals, NK3 is distributed in the brain, hypothalamus (including the median eminence), kidney, lung,
placenta, prostate, testis, muscle, intestine, uterus, and
the sperm midpiece as well as weakly in the proximal
region of the sperm flagellum. In zebrafish, tacr3a is
expressed mainly in the pituitary, also during embryonic
development. A low tacr3b expression was detected in
the midbrain and testis. In mammals, circulating NKB
via the enhancement of expression of the tac3 gene was
elevated in the placenta of preeclampsia women, but
not in the placenta of women in normotensive pregnancy. Moreover, NKB participates in the regulation
of GnRH pulse generation in the mammalian
hypothalamus-pituitary-gonad axis. This GnRH
release system is in part regulated by NKB in concert with
kisspeptin yielded by KNDy neurons, whereas the
involvement of non-KNDy NKB neurons or other
kisspeptin-free NKB neurons in the stimulation of GnRH
release is also reported. NK3R is also suggested to influence alcohol intake and behavioral/neurochemical
responses to cocaine. In prepubertal zebrafish, estradiol
treatment upregulates tac3a gene expression as well as
kiss1, kiss2, and gnrh3.? Furthermore, in sexually mature
zebrafish, the intraperitoneal injection of NKBa and
NKF resulted in the secretion of luteinizing hormone.
Clinical implications
NKB is highly likely to be involved in preeclampsia in the placenta and familial hypogonadotropic
hypognadism.
Biochem/physiol Actions
Neurokinin B is a ten-residue peptide. It is an endogenous tachykinin agonist with preference for the NK-3 receptor. It is a potent bronchoconstrictor and may have a neuromodulatory role in the brain. Neurokinin B has a role in slow synaptic or non-synaptic communication.
Check Digit Verification of cas no
The CAS Registry Mumber 86933-75-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,6,9,3 and 3 respectively; the second part has 2 digits, 7 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 86933-75:
(7*8)+(6*6)+(5*9)+(4*3)+(3*3)+(2*7)+(1*5)=177
177 % 10 = 7
So 86933-75-7 is a valid CAS Registry Number.
InChI:InChI=1/C55H79N13O14S2/c1-30(2)21-38(50(77)62-36(47(57)74)17-19-83-5)61-43(69)28-59-55(82)46(31(3)4)68-54(81)40(23-33-15-11-8-12-16-33)65-51(78)39(22-32-13-9-7-10-14-32)64-53(80)42(26-45(72)73)67-52(79)41(24-34-27-58-29-60-34)66-49(76)37(18-20-84-6)63-48(75)35(56)25-44(70)71/h7-16,27,29-31,35-42,46H,17-26,28,56H2,1-6H3,(H2,57,74)(H,58,60)(H,59,82)(H,61,69)(H,62,77)(H,63,75)(H,64,80)(H,65,78)(H,66,76)(H,67,79)(H,68,81)(H,70,71)(H,72,73)
86933-75-7Relevant articles and documents
NEUROKININ &α AND &β, SYNTHESIS AND PHARMACOLOGICAL PROPERTIES
Munekata, Eisuke,Okada, Masahiro,Kimura, Sadao,Sugita, Yoshiki,Kanazawa, Ichiro,et al.
, p. 1013 - 1016 (2007/10/02)
Two novel neuropeptides, neurokinin α and β, isolated from porcine spinal cord were chemically synthesized by solution method.The amino acid sequences proposed were confirmed to be correct and pharmacological properties of neurokinin peptides were studied
