피부신경펩티드에 의한 비만세포 활성화에 대한 연구

나영천,채옥희,송창호 대한해부학회 2009 Anatomy & Cell Biology Vol.42 No.3

Neuropeptides are widely distributed throughout skin, gastrointestinal tracts, and nervous and immune systems. Neuropeptides act to mediate the vasodilation and induce mast cell activation in humans and rats in vitro. However, the mechanism of the cutaneous neuropeptides-induced mast cell activation and the extent of the vascular permeability by cutaneous neuropeptides are not fully understood. This issue was investigated by the injecting six cutaneous neuropeptides-atrial natriuretic peptide, calcitonin gene-related peptide, neuropeptide Y, somatostatin, substance P and vasoactive intestinal peptide-into the skin of rats and by treatment of six cutaneous neuropeptides in rat peritoneal mast cell (RPMC) in vitro. All of the cutaneous neuropeptides increased the significant vascular permeability by the injection into the back skin of normal rats. All of the cutaneous neuropeptides also induced the mast cell degranulation and the histamine release from RPMCs, in a dose-dependent pattern, and increased the calcium uptake and decreased the level of cAMP of RPMCs in vitro. The effects of cutaneous neuropeptides on the vascular permeability and mast cell activation were inhibited by mast cell stabilization agent, disodium cromoglycate. These findings show that cutaneous neuropeptides can induce the mast cell activation by not only increasing the calcium uptake and decreasing the level of cAMP in RPMCs, but also the increment of vascular permeability in the skin of rats. 여섯 종류의 피부신경펩티드들 ANP, CGRP, NY, SOM, SP, VIP를 사용하여 피부에서 이들이 혈관투과성 증가 유 무와 비만세포의 활성화에 미치는 영향을 밝히고자 연구를 실시하여 다음과 같은 결과를 얻었다. 첫째, 여섯 종류의 피 부신경펩티드 모두 피부에서 혈관 투과성을 증가시켰다. 둘 째, 6종의 피부신경펩티드 모두 비만세포의 탈과립을 유발 하였다. 셋째, 6종의 피부신경펩티드 모두 비만세포로부터히스타민을 농도 의존적으로 유리시켰다. 넷째, 피부신경펩 티드 모두 비만세포의 칼슘 유입을 증가시켰다. 다섯째, 피 부신경펩티드 모두 비만세포의 cAMP 수준을 감소시켰다. 여섯째, 상기한 6종의 피부신경펩티드에 의한 비만세포의 활성화와 피부 혈관투과성 증가가 DSCG 전처리로 억제되 었다. 이상의 연구결과로 이들 피부신경펩티드들에 의한 피부 의 혈관투과성의 증가는 비만세포의 활성화에 기인할 것으 로 생각된다. 또한 피부신경펩티드는 비만세포내로의 칼슘 유입을 증가시키고, 세포내 cAMP 수준을 감소시켜 비만세 포의 활성화를 유발할 것으로 생각한다. 비만세포 안정화 물질(DSCG)이 피부신경펩티드에 의한 혈관 투과성 증가와 비만세포의 활성화를 억제하는 것으로 미루어, 신경펩티드 들과 비만세포들의 상호작용으로 유발되는 만성피부질환 등의 치료제로 비만세포 안정화 물질들을 사용할 수 있을 것으로 생각한다.

흰쥐 뇌에서 Neuropeptide-Y 분비세포의 출현시기 및 발육에 관한 면역조직화학적 연구

모근석,김종중,정윤영,장인엽,문정석,김준수,김흥중 대한해부학회 1996 Anatomy & Cell Biology Vol.29 No.5

Starfish smooth muscle relaxing activity of SALMFamide isotype peptide and its analog derived from starfish, Asterias rubens

Anastasia Kubarova,고혜진,오혜영,박남규 한국수산과학회 2022 Fisheries and Aquatic Sciences Vol.25 No.11

An organism’s physiological processes and behaviors are regulated by neuropeptides and hormone peptides. The first neuropeptide identified from echinoderms is SALMFamide. The two most well-studied SALMFamide neuropeptides are S1 and S2, which possess myoactivity on apical muscle, tube feet, and the cardiac stomach of starfishes. However, neuropeptide candidates identified from SALMFamide’s precursor protein sequence have not been investigated. This study aims to compare the bioactivity of SALMFamide neuropeptides from the starfish Asterias rubens using various starfish muscle preparations. In this study, the bioactivity of the L-type SALMFamide neuropeptides from the starfish A. rubens, AYHTGLPFamide (SALMFa-A) and the derivative AYHSALMFamide (SALMFa-B) was investigated. The neuropeptides were applied on Asterias amurensis apical muscle, tube feet, which revealed that the neuropeptides exhibit relaxing activity on apical muscle but no activity on tube feet. The native SALMFa- A peptide had lower relaxing activity on the apical muscle compared to the derivative peptide SALMFa-B. The relaxing activity of two neuropeptides also was compared with those on the apical muscle of Patiria pectinifera, which revealed relaxing activity as well as SALMFamide-S1 and S2 neuropeptides. Moreover, the investigation of SALMFa-A and SALMFa-B peptides’ bioactivity on P. pectinifera cardiac stomach muscle also showed slight relaxing activity.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

( Michael Furlong ),( Jae Young Seong ) 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.1

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

화상창상의 치유 및 반혼형성 과정에서 신경펩티드의 변화

장영철,범진식,이종욱,오석준 대한화상학회 2003 대한화상학회지 Vol.6 No.2

Perspective : Role of neuropeptide Y in the bone marrow hematopoietic stem cell microenvironment

( Min Hee Park ),( Woo Kie Min ),( Hee Kyung Jin ),( Jae Sung Bae ) 생화학분자생물학회 2015 BMB Reports Vol.48 No.12

The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) functions such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study, we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy- induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction in spite of NPY injection. Transforming growth factor-beta (TGF-β) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in the bone marrow. Therefore, this study reveals a new role of NPY in bone marrow HSC microenvironment, and provides an insight into the therapeutic application of this neuropeptide. [BMB Reports 2015; 48(12): 645-646]

Acute Effects of Glucagon-Like Peptide-1 on Hypothalamic Neuropeptide and AMP Activated Kinase Expression in Fasted Rats

SEO, Sanghee,JU, Sunghee,CHUNG, Hyunju,LEE, Dahm,PARK, Seungjoon The Japan Endocrine Society 2008 Endocrine journal Vol.55 No.5

<P>Intracerebroventricular (icv) administration of glucagon-like peptide-1 (GLP-1) inhibits food intake and induces c-fos expression in the hypothalamus. However, the effects of GLP-1 on hypothalamic neuronal activity or neuropeptide mRNA expression are unknown. In this study, we examined the effects of GLP-1 on fasting-induced changes in the expression of hypothalamic orexigenic and anorexigenic neuropeptide. Food intake was significantly inhibited after icv injection of GLP-1 in 48 h fasted rats. Hypothalamic neuropeptide Y (NPY) and agouti-related peptide (AgRP) mRNAs were significantly increased by fasting, whereas icv GLP-1 treatment significantly attenuated these fasting-induced increases. Both proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA levels were decreased by fasting, while GLP-1 treatment attenuated fasting-induced decreases in POMC and CART expression. We also determined the mRNA levels of AMP-activated kinase (AMPK) and found that fasting resulted in a significant stimulation of hypothalamic AMPKα2 mRNA. Fasting-induced increase in AMPKα2 mRNA was almost completely prevented by GLP-1 treatment. Analysis of phosphorylated AMPKα and acetyl CoA carboxylase showed similar results. Taken together, our observation suggests that the decreased food intake by GLP-1 is caused by preventing the fasting-induced increase in hypothalamic NPY and AgRP and the fasting-induced decrease in hypothalamic POMC and CART. Our results also suggest that the food intake lowering effect of GLP-1 is caused by reversing the fasting-induced increase in hypothalamic AMPK activity. Therefore we conclude that the anorectic effect of GLP-1 seems to be mediated by, at least in part, by the hypothalamus.</P>

방사선 조사 후 대뇌결질에 분포한 Neuropeptide-Y 양성신경세포에 관한 면역조직화학적 연구

이상욱,김종중,정윤영,정종달,오윤경 조선대학교 2000 The Medical Journal of Chosun University Vol.25 No.2

Background and Objectives : Severe irradiation on the cerebral cortex of the human and animals may result in functional alterations of central nervous system. The purpose of this study, the irradiation effects on the cerebral cortex of the rats after brain irradiation was to investigate the change of distribution and morphology of neuropeptide-Y(NPY) neurons. Materials and Methods : Radiation was produced by the linear accelerator 6MV X-ray, and the animals were categorized into control and experimental groups and we use 45 Sprague-Dawley rats weighing about 200~250gm. The head areas of the animals were positioned within the radiation field of 12㎝ × 20㎝ and with the radiation depth of 1.5㎝. Sodium chloral hydrate-anesthetized rats were exposed to the radiation with the dose rate of 240 cGy/min. The total dose was 1800 cGy. Animals were sacrificed on 2 hours, 5 hours, 1 day, 3 days, 7days after brain irradiation. Under anesthesia, animals were perfused with 4% paraformaldehyde-1% glutaraldehyde solution. On one or two hours after the perfusion, brain were taken out and refixed over night in the same fixative. Using ABC immunohistochemistry, morphology and distribution of neuropeptide-Y immunoractive(NPY-IR) neurons were studied on the cerebral cortex of the control and brain-irradiated rats. We used light, transmission electron and confocal laser scanning microscope. Results : The following results were obtained : 1. On control group, NPY-IR neurons were found in all layers of the primary sensory and motor cerebral cortex, and the NPY-IR neurons were concentrated within the layer II, III, IV, V and VI. The typical NPY-IR perikarya was bipolar and multipolar shape. 2. On 2 hours, 5 hours, 1 day after X-irradiation, decreased number of NPY-IR neurons were detected in the primary sensory and motor cerebral cortex of the rats. Also shrunken and transformed NPY-IR neurons were detected in the primary sensory and motor cerebral cortex of the rats. 3. On 3 days and 7 days after X-irradiation, morphology and distribution of NPY-IR neurons in the primary sensory and motor cerebral cortex was generally restored. 4. In optical serial section analysis of NPY-IR neurons, high fluorescence intensity were observed in a part of the 8~11 sections of the control and all irradiated groups. In optical single section analysis of NPY-IR neurons, red color(high fluorescence intensity) was observed in a part of 6, 7 sections of the control and all irradiated groups. 5. By electron microscopy, NPY-IR neurons on 2 hours, 5 hours, 1 day after X-irradiation rats exhibited severe alterations of their organelles concerning intracellular material transport ; such as disappearance of microvilli and basal infoldings, reduction of invaginating pits on the basal and apical plasma membranes, reduction of transformed vesicles and shrunken Golgi complexes, etc. Conclusion : From the above results, it was concluded that the release of neurotransmitters and transcapillary leakage of blood substance were occurred on 2 hours, 5 hours, 1 day after X-irradiation, but the condition was generally restored on 3 days and 7 days following X-irradiation.

Effects of Substance P and VIP on the Alkaline Phosphatase Activity and the Gene Expression of Bone Proteins in Osteoblast-like Cells

Oh, Jun Hie,Choi, Byung Ju The Official Publication of Korean Academy of Oral 1995 International Journal of Oral Biology Vol.19 No.1

This study was performed to determine whether bone cells responded directly to substance P and VIP and to elucidate how bone formation and resoption was regulated by these neuropeptides. The activity of ALP and the gene expressions of bone secific proteins (integrin beta 1, osteocalcin, and OSF) were measured using MC3T3-E1 cell lines as in vitro bone model system. In present study, cells were subcultured, seeded and grown for 10 days. To screen out neuropeptides that had effects on ALP activity, we stimulated cells with CGRP, neuropeptide Y, proenkephalin A, substance P and VIP with concentrations of 10-7 M. ALP activities stimulated by substance P and VIP were significantly inhibited from 11.02±0.72 nM/㎎ protein/min to 7.91±0.66, 8.04±0.70, respectively (p<0.01). But these ALP inhibitions were not shown in cells stimulated with CGRP, neuropeptide Y, and proenkephalin A. The dose-re-lated dffects of substance P and VIP on ALP activities were ont shown. To determine whether substance P and VIP affect the mRNA expressions of bone specific proteins, we evaluated RT-PCR products using primers of integrin beta 1, osteocalcin, and OSF. No significant changes in mRNA expressions of these bone proteins were observed. These results suggest that substance P and VIP may play significant roles in regulation of bone metabolism, especially in ALP cativities. In addition, these neuropeptides may exert effects on the synthesis of bone proteins.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

Furlong, Michael,Seong, Jae Young The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.1

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.