• Title/Summary/Keyword: activating receptor

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The Effects of Hantaan Virus on the Expression of Platelet Activating Factor Receptor and on the Activity of Platelet Activating Factor Acetylhydrolase (한탄바이러스가 혈소판활성인자 수용체 발현 및 혈소판활성인자 분해효소 활성에 미치는 영향)

  • Hwang, Ji-Young;Park, Jong-Won;Hong, Sae-Yong;Park, Ho-Sun
    • Journal of Yeungnam Medical Science
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    • v.25 no.1
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    • pp.41-49
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    • 2008
  • Background : The central physiological derangement of hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) is a vascular dysfunction, manifested by hemorrhage, impaired vascular tone and increased vascular permeability. Platelet activating factor (PAF), whose actions are mediated through a specific receptor, is a potent bioactive lipid. PAF has diverse biological functions in the vascular system, such as increasing vascular permeability, adhesion of leukocytes to the endothelium and reduction of cardiac output, which result in hypotension and shock. The goal of the present study was to investigate whether PAF is involved in the pathogenesis of HFRS. For this purpose, we evaluated the effect of HTNV on the expression of PAF receptor (PAF-R) and on the activity of PAF-acetylhydrolase (PAF-AH) instead of PAF because PAF is rapidly degraded by PAF-AH in vivo. Materials and methods : To evaluate the expression of PAF-R, we performed reverse-transcription PCR, western blot and FACS analyses using HTNV-infected human umbilical vein endothelial cells (HUVECs) and non-infected (control) HUVECs. In addition, we measured the activity of plasma PAF-AH in HFRS patients and normal healthy persons. Results : The mRNA and protein expression of PAF-R was increased in HTNV-infected HUVECs compared with control HUVECs at 2 and 3 days post-infection (d.p.i.). FACS analysis showed that HTNV induced the surface expression of PAF-R in HUVECs from 2 d.p.i. The activity of plasma PAF-AH was 2.5-fold lower in HFRS patients than in normal healthy persons. Conclusion : Increased PAF-R expression by HTNV might increase the responsiveness to PAF in endothelial cells. Reduced PAF-AH activity in the blood of HFRS patients might delay PAF degradation. These results suggest that changes in PAF-R and PAF-AH by HTNV might influence to PAF activity and might be involved in the vascular dysfunction of HFRS.

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Screening of the Platelet Activating Factor(PAF) Antagonistic Activities on Herbal Medicines (생약의 물 추출물에 대한 혈소판 활성화인자 수용체 결합 저해활성 검색)

  • Han, Byung-Hoon;Yang, Hyun-Ok;Kim, Yong-Chul;Han, Yong-Nam
    • YAKHAK HOEJI
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    • v.38 no.4
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    • pp.462-468
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    • 1994
  • Hot aqueous extracts of 130 herbal medicines were screened for platelet activating factor (PAE) receptor binding antagonistic activity using rabbit platelet. The results suggested that 4 medicinal plants including Biota orientalis are potential sources of PAF antagonists.

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Progress of Pruritus Research in Atopic Dermatitis

  • Lee, Chang-Hoon
    • Biomolecules & Therapeutics
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    • v.18 no.3
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    • pp.246-256
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    • 2010
  • Atopic dermatitis is a common skin disease affecting up to 10% of children and approximately 2% of adults. Atopic dermatitis exhibits four major symptoms, including intense itching, dry skin, redness and exudation. The "itch-scratch-itch" cycle is one of the major features in atopic dermatitis. The pathophysiology and neurobiology of pruritus is unclear. Currently there are no single and universally effective pharmacological antipruritic drugs for treatment of atopic dermatitis. Thus, controlling of itch is a very important unmet need in patients suffering from atopic dermatitis. This article will update progress during the past 10 years of research in the field of pruritus of atopic dermatitis, focusing on aspects of pruritogens (including inflammatory lipids, histamine, serotonin, proteinases, proteinase-activating receptors, neurotransmitters, neuropeptides, and opioid peptides), antipruritic therapies, and emerging new targets. Based on recent progress, researchers expect to identify exciting possibilities for improved treatments and to develop new antipruritic drugs acting through novel targets, such as histamine H4 receptor, gastrin-releasing peptide receptor, MrgprA3, thromboxane A2 receptor and the putative SPC receptor.

Inhibition of THIP on Morphine-Induced Hyperactivity, Reverse Tolerance and Postsynaptic Dopamine Receptor Supersensitivity

  • Oh, Ki-Wan;Yoon, In-Seup;Shin, Im-Chul;Hong, Jin-Tae;Lee, Myung-Koo
    • Archives of Pharmacal Research
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    • v.25 no.2
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    • pp.202-207
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    • 2002
  • This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a $GABA_A$ agonist, on the morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a reverse tolerance to the hyperactivity caused by morphine (10 mg/kg ,s.c.). THIP inhibited the development of reverse tolerance in the mice that had received the repeated same morphine (10 mg/kg s.c.) doses. The postsynaptic dopamine receptor supersensitivity, which was evidenced by the enhanced ambulatory activity its after the administration of apomorphine (2 mg/kg s.c.), also developed in the reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity indulged by the chronic morphine administration. These results suggest that the hyperactivity, reverse toterance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the $GABA_A$ receptors.

Mouse Nerve Growth Factor Facilitates the Growth of Interspinal Schwannoma Cells by Activating NGF Receptors

  • Liu, Shu Yi;Liu, Sheng Ze;Li, Yu;Chen, Shi
    • Journal of Korean Neurosurgical Society
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    • v.62 no.6
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    • pp.626-634
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    • 2019
  • Objective : Nerve growth factor (NGF) is a member of the neurotrophic factor family and plays a vital role in the physiological processes of organisms, especially in the nervous system. Many recent studies have reported that NGF is also involved in the regulation of tumourigenesis by either promoting or suppressing tumor growth, which depends on the location and type of tumor. However, little is known regarding the effect of NGF on interspinal schwannoma (IS). In the present study, we aimed to explored whether mouse nerve growth factor (mNGF), which is widely used in the clinic, can influence the growth of interspinal schwannoma cells (ISCs) isolated from IS in vitro. Methods : ISCs were isolated, cultured and identified by S-100 with immunofluorescence analysis. S-100-positive cells were divided into five groups, and separately cultured with various concentrations of mNGF (0 [phosphate buffered saline, PBS], 40, 80, 160, and 320 ng/mL) for 24 hours. Western blot and quantantive real time polymerase chain reaction (PCR) were applied to detect tyrosine kinase A (TrkA) receptor and p75 neurotrophin receptor ($p75^{NTR}$) in each group. Crystal violet staining was selected to assess the effect of mNGF (160 ng/mL) on ISCs growth. Results : ISCs growth was enhanced by mNGF in a dose-dependent manner. The result of crystal violet staining revealed that it was significantly strengthened the cells growth kinetics when cultured with 160 ng/mL mNGF compared to PBS group. Western blot and quantantive real time PCR discovered that TrkA receptor and mRNA expression were both up-regualated under the condition of mNGF, expecially in 160 ng/mL, while the exoression of $p75^{NTR}$ demonstrated no difference among groups. Conclusion : From these data, we conclude that exogenous mNGF can facilitate ISC growth by activating both TrkA receptor and $p75^{NTR}$. In addition, patients who are suffering from IS should not be administered mNGF in the clinic.

Mutations of Constitutive Activation and Mutations That Impair Signal Transduction Modulate the Agonist-stimulated Internalization of the Lutropin/choriogonadotropin Receptor

  • Park, J.J.;Kim, M.S.;Lee, Y.Y.;H.Y. Kang;Y.M. Chang;Yoon, J.T.;K.S. Min
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.83-83
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    • 2003
  • The lutropin/choriogonadotropin receptor (LHR) is a member of the rhodopsin-like subfamily of G protein coupled receptor (GPCRs), that has been shown to mediate the internalization of its two naturally occurring agonist, lutropin and choriogonadotropin (CG). The clustered agonist-receptor complex is internalized by a dynamin-dependent pathway and traverses the endosomal compartment without agonist dissociation Dissociation of the agonist-receptor complex occurs in the lysosomes, where both the agonist and receptor are degrade. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty (FMPP). A FMPP is a form of sexual precocious puberty in boys in which testosterone levels are elevated independent of changes in luteinizing hormone-releasing hormone and serum luteinizing hormone levels, We have now analyzed two naturally occurring, constitutively active mutants of the human LHR. These mutations were introduced into the rat LHR (rLHR) and are designated L435R and D556Y. Cells expressing rLHR-D556Y bind human choriogonadotropin (hCG) with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. Cells expressing rLHR-L435R also bind hCG with normal affinity, exhibit a 47-fold increase in basal cAMP, and do not respond to hCG with a further increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17- fold, respectively We conclude that the state of activation of the rLHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing rLHR-L435R is due to the fast rate of internalization of the bound hCG. The finding that membranes expressing rLHR-L435R respond to hCG with an increase in adenylyl cyclase activity supports this suggestion. Autonomous Leydig cell activity in FMPP is caused by a constitutively activating LH/CGR.

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Satellite Cells Isolated from Adult Hanwoo Muscle Can Proliferate and Differentiate into Myoblasts and Adipose-like Cells

  • Kook, Sung-Ho;Choi, Ki-Choon;Son, Young-Ok;Lee, Kyung-Yeol;Hwang, In-Ho;Lee, Hyun-Jeong;Chang, Jong-Soo;Choi, In-Ho;Lee, Jeong-Chae
    • Molecules and Cells
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    • v.22 no.2
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    • pp.239-245
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    • 2006
  • This study examined whether adult bovine muscle satellite cells from 30-month-old Hanwoo cattle are multipotential. The satellite cells were found to have the potential to proliferate and differentiate into myoblasts with the formation of multinucleated cells. In addition, treatment with the peroxisome proliferator activating receptor-${\gamma}$ ($PPAR{\gamma}$) agonist, rosiglitazone, promoted their trans-differentiation into adipocytes with significant increases in glycerol accumulation and glycerol-3-phosphate dehydrogenase activity. Western blot analysis revealed that increased levels of the adipocyte fatty acid-binding protein, $PPAR{\gamma}$ and of CCAAT/enhancerbinding protein were closely related to rosiglitazoneinduced differentiation of the cells. These findings demonstrate that satellite cells from adult Hanwoo cattle are multipotent, and that their trans-differentiation into adipocytes can be induced by rosiglitazone.