• Bulletin of the Korean Chemical Society
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• v.21 no.9
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• pp.932-934
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• 2000

• Proceedings of the Zoological Society Korea Conference
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• 1998.10b
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• pp.223.2-223
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• 1998

No Abstract, See Full Text

• Proceedings of the Korean Biophysical Society Conference
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• 1999.06a
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• pp.31-31
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• 1999

Neuropeptide ${\gamma}$ is a recently identified tachykinin family peptide which has conserved ammo acid sequence of -Phe-X-Gly-Leu-Met-NH2 in the C-terminal region, where X represents aromatic or hydrophobic residues. In this study, three-dimensional structure of neuropeptide ${\gamma}$ from goldfish Carassius auratus (G-NP${\gamma}$) was determined by NMR spectroscopy.(omitted)

• BMB Reports
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• v.29 no.5
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• pp.429-435
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• 1996

To investigate the structure-antagonistic relationship of the cyclohexapeptide L-659,877, a selective NK-2 tachykinin receptor antagonist, seven analogues were chemically synthesized by a solid phase method. The agonistic and antagonistic activities of the analogues were evaluated by contraction assay using the smooth muscle of guinea pig trachea (GPT) containing the NK-2 receptor. It was shown that the aromatic ring of Phe at position 3 and the sulfur group of Met at position 6 in L-659,877 were essential for binding to the NK-2 receptor. Decrease in antagonistic activity of L-659,877 caused by substituting Leu for Nle at position 5 indicates that the ${\gamma}$ methyl group and side chain length of Leu plays an important role in its antagonistic action. Although the activity was slightly lower than L-659,877, cyclo $[{\beta}Ala^{8}]NKA(4-10)$ (analogue 1) showed potential antagonistic activity for the NK-2 receptor. It was confirmed that the expansion of the ring in L-659,877 by substitution of ${\beta}Ala$ for Gly at position 4 stabilized its conformation monitored by CD spectra. The results suggest that analogue 1 can be used as a new leader compound to design a more powerful, selective, and stable NK-2 receptor antagonist.

• Clinical and Experimental Pediatrics
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• v.65 no.4
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• pp.172-181
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• 2022

Pubertal onset is known to result from reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, which is controlled by complex interactions of genetic and nongenetic factors. Most cases of precocious puberty (PP) are diagnosed as central PP (CPP), defined as premature activation of the HPG axis. The cause of CPP in most girls is not identifiable and, thus, referred to as idiopathic CPP (ICPP), whereas boys are more likely to have an organic lesion in the brain. ICPP has a genetic background, as supported by studies showing that maternal age at menarche is associated with pubertal timing in their offspring. A gain of expression in the kisspeptin gene (KISS1), gain-of-function mutation in the kisspeptin receptor gene (KISS1R), loss-of-function mutation in makorin ring finger protein 3 (MKRN3), and loss-of-function mutations in the delta-like homolog 1 gene (DLK1) have been associated with ICPP. Other genes, such as gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), lin-28 homolog B (LIN28B), neuropeptide Y (NPYR), tachykinin 3 (TAC3), and tachykinin receptor 3 (TACR3), have been implicated in the progression of ICPP, although their relationships require elucidation. Environmental and socioeconomic factors may also be correlated with ICPP. In the progression of CPP, epigenetic factors such as DNA methylation, histone posttranslational modifications, and non-coding ribonucleic acids may mediate the relationship between genetic and environmental factors. CPP is correlated with short- and long-term adverse health outcomes, which forms the rationale for research focusing on understanding its genetic and nongenetic factors.

• Journal of fish pathology
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• v.14 no.1
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• pp.46-53
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• 2001

The present study was undertaken to investigate and compare the effect and mode of action of tachykinins on isolated strip preparations of the intestinal smooth muscle from the nile tilapia, Oreochromis niloticus and the Israel carp, Cyprinus carpio. Both of neurokinin 1(NK-1) receptor agonist, substance P(SP) and neurokinin 2(NK-2) receptor agonist, neurokinin A(NKA) caused concentration-dependent contractions of intestinal smooth muscle in the nile tilapia and the israel carp. The efficiency and potency of these agonists varied between two fish species. In the nile tilapia intestine, the efficiency and potency of SP were greater than those of NKA. However, the efficiency and potency of SP were similar to those of NKA. In the nile tilapia intestine and the israel carp intestine, the contractile responses of SP and NKA were noncompetitively antagonized by NK-1 receptor antagonist, L-732, 138 but unaffected by NK-2 receptor antagonist, MDL 29913. In addition, SP-induced contractions in the both of preparation were significantly inhibited by muscarinic antagonist, atropine($5{\times}10^{-7}$M) and ganglionic inhibitor, tetrodotoxin($2{\times}10^{-7}$M) but NKA-induced contractions were unaffected by those. These results indicate that two tachykinin agonists, SP and NKA predominately modulate the mechanical activity of isolated preparation from the nile tilapia and the israle carp directly through the activation of NK-1 receptor on the intestinal smooth muscle cells, but in the case of SP action, the indirect action through activation of cholinergic nerve terminals seems to be also implicated.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.139-146
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• 1997

In the present study, capsaicin-induced desensitization of peripheral sensory nerves were investigated by using guinea pig bronchi, in which these nerves are stimulated with cap saicin to produce a contractile response via the release of sensory neuropeptides such as substance P and neurokinin A. The contractile response to capsaicin was inhibited by the combination of CP96345 and SR 48968 suggesting that the excitatory effect of capsaicin is mediated via both the tachykinin NK-1 and NK-2 receptor. Capsaicin produced in vitro-desensitization in dose-dependent manner, but after this in vitro-desensitization the response to NK-1 and NK-2 receptor agonist did not change. Systemic administration (s.c.) of capsaicin also desensitized significantly bronchial tissues but could not produce any change in the contractile response to the selective agonists of NK-1 and NK-2 receptor. Therefore, the present results suggest that functional desensitization to capsaicin-induced contractile response in guinea pig bronchi does not involve NK-1 and NK-2 receptor, while excitatory effect of capsaicin is mediated via both NK-1 and NK-2 receptor. In conclusion, it is suggested that capsaicin- induced excitation and desensitization involves somewhat different pathways.

• Development and Reproduction
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• v.20 no.1
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• pp.51-61
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• 2016

Neurokinin B (NKB) and neurokinin B related peptide (NKBRP) belong to tachykinin peptide family. They act as a neurotransmitter and/or neuromodulator. Mutation of NKB and/or its cognate receptor, NK3R resulted in hypogonadotropic hypogonadism in mammals, implying a strong involvement of NKB/NK3R system in controlling mammalian reproduction. Teleosts possess NKBRP as well as NKB, but their roles in fish reproduction need to be clarified. In this study, NKB and NKBRP coding gene (tac3) was cloned from Nile tilapia and sequenced. Based on the sequence, Nile tilapia NKB and NKBRP peptide were synthesized and their biological potencies were tested in vitro pituitary culture. The synthetic NKBRP showed direct inhibitory effect on the expression of GTH subunits at the pituitary level. This inhibitory effect was confirmed in vivo by means of intraperitoneal (ip) injection of synthetic NKB and NKBRP to mature female tilapia (20 pmol/g body weight [BW]). Both NKB and NKBRP had no effect on the plasma level of sex steroids, E2 and 11-KT. However, NKBRP caused declines of expression level of GnRH I, Kiss2 and tac3 mRNAs in the brain while NKB seemed to have no distinct effect. These results indicate some inhibitory roles of NKBRP in reproduction of mature female Nile tilapia, although their exact functions are not clear at the moment.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.805-818
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• 1997

Immune responses of periodontal tissue may be regulated by products of sensory afferent nerve endings such as neuropeptides. Substance P(SP), a tachykinin neuropeptide, has been previously reported to stimulate the activities of T lymphocyte. Therefore, I examined the role of SP in IL-2 production and cell proliferation by using a homogeneous line of T lymphocytes(Jurkat and HuT78). Cell proliferation rate was determined by [$^3H$]-thymidine incorporation test, and IL-2 was quantitated by the growth rate of CD4+ IL-2-dependent T lymphocyte line CTLL-2. SP stimulated cell proliferation of T lymphocytes at the concentration of $10^{-12}$ and $10^{-8}$M in a biphasic bell-shape dose-dependent manner. However, SP alone did not induce IL-2 release at the concentration range of $10^{-6}$ to $10^{-14}$M. The upregulation of IL-2 release was observed when $10^{-12}$M SP was applied together with mitogens such as Con A or PHA+PMA on T cell lines, especially on Jurkat. Con A or PHA+PMA demonstrated to increase the rate of cell proliferation of Jurkat, which had shown to produce much amount of IL-2 indicating that mitogen-induced cell proliferation might be partially influenced by released IL-2. It was concluded that regulatory effects of SP on the immune/inflammatory response could be mediated through the costimulatory upregulation of IL-2 production and increase of cell proliferation of T lymphocyte.

• Journal of the Korean Chemical Society
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• v.43 no.5
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• pp.540-546
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• 1999

Solution conformation of cyclo-($Gln^1-Trp^2-Phe^3-{\beta}Ala^4-Leu^5-Met^6$), new NK-2 antagonist in dimethyl sulfoxide solution, has been determined by the use of two-dimensional nuclear magnetic resonance spectroscopy combined with simulated annealing calculations. The peptide exhibited converged structures with the atomic root-mean-square difference for the backbone atoms ($N,\;C^{\alpha},\;C'$) of all residues being 0.02${\AA}$ in the 25 annealed structures. The analysis of the structures indicated that the cyclic peptide has three intramolecular hydrogen bonds between $Met^6NH$ and ${\beta}Ala^4CO$, ${\beta}Ala^4NH$ and $Met^6CO$, $Phe^3NH$ and $Met^6CO$, and contain a type-I ${\beta}$-turn with Gln and Trp and ${\gamma}$-turn with Leu. The addition of an extra methylene group to Gly, i.e. P-Ala residue, may relax some unfavorable restraints in the cyclic backbone structure, hence enabling an additional hydrogen bond, which results in stabilizing one conformation.