• Bulletin of the Korean Chemical Society
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• 제21권9호
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• pp.932-934
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• 2000

• 한국동물학회:학술대회논문집
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• 한국동물학회 1998년도 한국생물과학협회 학술발표대회
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• pp.223.2-223
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• 1998

No Abstract, See Full Text

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
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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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• 제29권5호
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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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• 제65권4호
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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.

• 한국어병학회지
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• 제14권1호
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• pp.46-53
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• 2001

본 연구에서는 경골어류인 나일틸라피아(Oreochromis niloticus)와 이스라엘잉어(Cyprinus carpio)의 장관에 대한 neurokinin-1(NK-1)수용체 효능제인 substance p(SP)와 neurokinin-2(NK-2)수용체 효능제인 neurokinin A(NKA)의 수축활성과 작용기전을 비교 분석하였다. SP와 NKA는 모두 나일틸라피아와 이스라엘잉어의 장관 평활근에 대하여 농도 의존적인 수축반응을 나타내었다. 그러나 이들에 의한 수축반응의 경향은 어종에 따라 다르게 나타났다. 즉, 나일틸라피아 장관 평활근에 대하여서는 SP가 NKA에 비하여 높은 친화력과 효능을 나타내었으나, 이스라엘잉어의 장관 평활근에 대하여서는 SP와 NKA의 수축반응은 유의한 차이가 없었다. 나일틸라피아 및 이스라엘잉어의 장관 평활근에 대한 SP와 NKA의 수축반응들은 모두 NK-1 수용체 차단제인 L-732,138에 의해서는 비경쟁적으로 길항되었으나, NK-2 수용체 차단제인 MDL 29913에 의해서는 영향을 받지 않았다. 한편, 선택적 무스카린성 수용체 길항제인 atropine($5{\times}10^{-7}$M)및 신경절 차단제인 tetrodotoxin($2{\times}10^{-7}$M)은 나일틸라피아 및 이스라엘잉어의 장관 평활근에 있어서 SP에 의해 유발된 수축반응들은 모두 유의성 있게 억제시켰으나, NKA에 의해 유발된 수축반응들에 대하여서는 유의성 있는 영향을 나타내지 않았다. 이상의 결과들을 종합하여 보면, SP및 NKA는 모두 어류의 장관 평활근에 대하여 강력한 수축효과를 나타내나 그 작용기전은 다르다고 추정된다. 즉, SP및 NKA의 장관 수축작용은 주로 장관 평활근에 존재하는 NK-1 수용체를 매개한 직접적인 작용에 기인하는 것으로 사료되나 SP의 경우에는 tachykinin 수용체를 통한 직접작용 이외에도 콜린성 신경말단(cholinergic nerve terminal)을 자극하는 간접적인 경로도 관여하는 것으로 추정된다.

• 약학회지
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• 제41권1호
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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.

• 한국발생생물학회지:발생과생식
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• 제20권1호
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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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• 제27권4호
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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.

• 대한화학회지
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• 제43권5호
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• pp.540-546
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• 1999

새로운 NK-2 antagonist이며 고리상 펩티드인 cycIo-($Gln^1-Trp^2-Phe^3-{\beta}Ala^4-Leu^5-Met^6$)의 DMSO 용액 중에서의 형태를 2차원 핵자기공명과 분자동력학적인 계산에 의하여 결정하였다. 조건을 만족시키는 25개의 구조는 모든 아미노산 잔기의 골격원자들 (N,$C^{\alpha}$, C')의 자승 평균 평방근이 $0.02{\AA}$이내로 수렴하였다. 이 고리상 펩티드의 구조는 $Met^6NH$와 $Ala^4CO$, $Ala^4NH$와 $Met^6CO$, $Phe^3NH$와 $Met^6CO$의 사이에 분자내 수소결합이, Gln과 Trp에 type-I ${\beta}$-turn, 그리고 Leu에서 ${\gamma}$-turn을 취하고 있었다. 알려져 있는 고리상 펩티드인 cyclo-($Gln^1-Trp^2-Phe^3-Gly^4-Leu^5-Met^6$)의 Gly이 ${\beta}$Ala으로 바뀜에 따라 ${\beta}$Ala의 여분의 메틸렌이 고리의 골격의 반발력을 완화시키고 수소결합들이 형태의 안정에 기여하고 있다고 생각된다.