• Title/Summary/Keyword: P2 receptors

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Lipoteichoic Acid from Lactobacillus plantarum Inhibits the Expression of Platelet-Activating Factor Receptor Induced by Staphylococcus aureus Lipoteichoic Acid or Escherichia coli Lipopolysaccharide in Human Monocyte-Like Cells

  • Kim, Hangeun;Jung, Bong Jun;Jeong, Jihye;Chun, Honam;Chung, Dae Kyun
    • Journal of Microbiology and Biotechnology
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    • v.24 no.8
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    • pp.1051-1058
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    • 2014
  • Platelet-activating factor receptor (PAFR) plays an important role in bacterial infection and inflammation. We examined the effect of the bacterial cell wall components lipopolysaccharide (LPS) and lipoteichoic acid (LTA) from Lactobacillus plantarum (pLTA) and Staphylococcus aureus (aLTA) on PAFR expression in THP-1, a monocyte-like cell line. LPS and aLTA, but not pLTA, significantly increased PAFR expression, whereas priming with pLTA inhibited LPS-mediated or aLTA-mediated PAFR expression. Expression of Toll-like receptor (TLR) 2 and 4, and CD14 increased with LPS and aLTA treatments, but was inhibited by pLTA pretreatment. Neutralizing antibodies against TLR2, TLR4, and CD14 showed that these receptors were important in LPS-mediated or aLTA-mediated PAFR expression. PAFR expression is mainly regulated by the nuclear factor kappa B signaling pathway. Blocking PAF binding to PAFR using a PAFR inhibitor indicated that LPS-mediated or aLTA-mediated PAF expression affected TNF-${\alpha}$ production. In the mouse small intestine, pLTA inhibited PAFR, TLR2, and TLR4 expression that was induced by heat-labile toxin. Our data suggested that pLTA has an anti-inflammatory effect by inhibiting the expression of PAFR that was induced by pathogenic ligands.

Effect of Banhasasimtang Granule on Gastric Emptying in Rats (흰쥐의 위(胃) 배출능(排出能)에 대한 반하사심탕(半夏瀉心湯)의 효능(效能))

  • Lee, Joon-Suk;Kim, Jin-Sung;Ryu, Bong-Ha;Yoon, Sang-Hyub
    • The Journal of Internal Korean Medicine
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    • v.27 no.2
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    • pp.471-479
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    • 2006
  • Backgrounds & Objectives: Banhasasimtang granule(BHSST) has been used for the treatment of functional dyspepsia regarded as one of the gastric dysmotility disease. but its mechanisms of action are not well known yet: So we investigated the effects of BHSST on gastric emptying and its mechanisms of action in rats. Methods: Gastric emptying was measured by glass beads(1mm in diameter) expelled from the stomach for 60 min after administration of normal saline(NS) or BHSST 31mg/kg or 93mg/kg in rats. And by the same method gastric emptying was measured after administration of NS or BHSST 93mg/kg in rats treated with atropine sulfate(1mg/kg, s.c.), quinpirol HCI(0.3mg/kg, i.p.), NAME(NG-nitro-L-arginine methyl ester, 75mg/kg, s.c.) or cisplatin(10mg/kg, i.p.) to make delayed gastric emptying. Results: BHSST 93mg/kg improved gastric emptying more than NS or BHSST 31mg/kg(p=0.016). Under the delayed gastric emptying, BHSST 93mg/kg improved gastric emptying in the group treated with NAME$(5.00{\pm}3.101\;vs\;9.00{\pm}3.51,\;p\;=0.046)$, but aggravated it With atropine sulfate$(5.71{\pm}3.45\;vs\;2.57{\pm}1.62,\;p\;=0.050)$ and cisplatin$(12.7{\pm}2.29\;vs\;8.57{\pm}5.06,\;p\;=0.072)$. Conclusions: BHSST improves the gastric emptying through cholinergic and 5-hydroxytryptamine 3 receptors. Especially it is effective to improve gastric emptying delayed by NAME. So we expect that it would be effective in functional dyspepsia with impaired reservoir functions such as gastric adaptive relaxation.

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Muscarinic Receptor Subtype Controlling the Carbachol-Induced Muscle Contraction in Guinea Pig Gastric Antrum

  • Rhee, Jong-Chul;Uhm, Dae-Yong;Kang, Tong-Mook
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.2
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    • pp.105-111
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    • 2000
  • Stimulation of muscarinic receptors by carbachol (CCh) in the circular smooth muscle of the guinea pig gastric antrum causes muscle contraction. In the present study, muscarinic receptor subtype controlling the muscle contraction in response to CCh was studied using putative muscarinic receptor antagonists. Isometric force of the isolated circular muscle strips was measured in an organ bath. CCh contracted the muscle in a dose-dependent way, and each of the three muscarinic receptor antagonists, 4-diphenylacetoxy- N-methylpeperdine methiodide (4-DAMP), methoctramine and pirenzepine shifted the concentration- response curves to the right without significantly reducing the maximum force. The affinities of the muscarinic antagonists $(pA_2\;values)$ obtained from Schild plot analysis were 10.15, 7.05 and 6.84 for 4-DAMP, methoctramine and pirenzepine, respectively. These results suggest that the $M_3-subtype$ mainly mediate the muscle contraction in response to CCh in guinea pig gastric antrum.

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NR3C1 Polymorphisms for Genetic Susceptibility to Schizophrenia

  • Park, Joo Seok;Lee, Sang Min;Kim, Jong Woo;Kang, Won Sub
    • Korean Journal of Biological Psychiatry
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    • v.26 no.2
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    • pp.88-93
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    • 2019
  • Objectives Psychological stress has been known to increase the risk of schizophrenia. Because stress responses are mainly mediated by cortisol, the action of the glucocorticoid receptors (Nuclear Receptor Subfamily 3 Group C Member 1, NR3C1) is possibly related to the pathogenesis of schizophrenia. In this study, we investigated the associations between polymorphisms of NR3C1 and schizophrenia. Methods Four single nucleotide polymorphisms (SNPs) (rs17100236, rs2963155, rs9324924, and rs7701443) of NR3C1 were genotyped in 208 patients with schizophrenia and 339 healthy individuals. A chi-square test was performed to test differences in allele distributions among groups. A multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and multiple inheritance models to analyze the associations between schizophrenia and SNPs (the dominant, recessive and additive models). Results The minor allele frequencies of two SNPs were significantly higher in the schizophrenia group than in those of the control group (rs2963155 G > A : 0.25 vs. 0.18, p = 0.0066 ; rs7701443 A > G : 0.40 vs. 0.33, p = 0.012). The genotype frequencies of two SNPs were found to be significantly different between patients with schizophrenia and controls in the dominant model (rs2963155 : AG/GG vs. AA, OR = 1.66, 95% CI = 1.16-2.38, p = 0.0055, rs7701443 : AG/AA vs. GG, OR = 1.61, 95% CI = 1.11-2.34, p = 0.01) and the log-additive model (rs2963155 : AG vs. GG vs. AA, OR = 1.54, 95% CI = 1.13-2.10, p = 0.0067). Conclusions This study showed significant associations between NR3C1 polymorphisms and schizophrenia. It suggests that NR3C1 may play a role in the pathogenesis of schizophrenia.

Effects of Endocrine Disruptors on the Expression of Estrogen Receptors in Ovary and Uterus from Immature Rats (내분비계 장애물질이 미성숙한 흰쥐의 난소와 자궁에서의 에스트로겐 수용체 발현에 미치는 효과)

  • Lee, Kyeung-Yeup;Lee, Sung-Ho
    • Development and Reproduction
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    • v.10 no.4
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    • pp.255-261
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    • 2006
  • Although some phytoes rogens might have beneficiary rather than adverse effects, most endocrine disrupting compounds(EDCs) are considered to be harmful to human and wildlife health through interfering the endocrine system. Previously we found that prepubertal exposure to genistein(GS), a well-known isoflavone phytoestrogen, could activate the reproductive system of immature female rats resulting precocious puberty. Interestingly, di(2-ethyl hexyl) phthalate(DEHP) exposure brought inverse result, a delayed puberty, in the same experimental regimen. In this study, we examined whether prepubertal exposure to GS or DEHP affect the gene expressions of estrogen receptors($ER\;{\alpha}$ and $ER\;{\beta}$) and LH receptor(LHR) which represent the maturational status of ovary and uterus in immature rats. GS (100 mg/kg/day) was administered daily from postnatal day 25 to the day when the first vaginal opening(VO) was observed, and the animals were sacrificed on the next day(day 32). Similarly, DEHP(l00 mg/kg/day) was administered daily from postnatal day 25 through the day when the first V.O. in control group was observed, and the animals were sacrificed on the next day(day 36). To determine the transcriptional changes in the hormone receptors, total RNAs were extracted from ovary and uterus and were applied to semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). In the GS group, the transcriptional activities of $ER\;{\alpha}$, $ER\;{\beta}$ and LHR in uterus and LHR in ovary were significantly increased when compared to those of control group. In the DEHP group, the transcriptional activities of all the hormone receptors measured were significantly lowered when compared to those of control group. These alteration of the reproductive hormone receptor expressions in ovary and uterus might be represent the phenotypic aspects(secondary sexual characteristics) such as tissue weights and reproductive hormone levels during perinatal period in immature female rats.

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Anti-allodynic Efficacy of NMDA Antagonist Peptide and Noradrenaline Alone and in Combination in Rodent Neuropathic Pain Model

  • Nasirinezhad, Farinaz;Hosseini, Marjan;Salari, Sajad
    • The Korean Journal of Pain
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    • v.28 no.2
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    • pp.96-104
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    • 2015
  • Background: The present experiment was conducted to identify the cooperative effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral neuropathic pain. Methods: Chronic constriction injury of the right sciatic nerve was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was inserted into the subarachnoid space. Acetone drops and a $44^{\circ}C$ water bath were used to evaluate the cold and heat allodynia, respectively. Placing and grasping reflexes were used to assess the locomotor system. Results: SHG at 0.5 and $1{\mu}g$significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and $1{\mu}g$(P < 0.001) of SHG. $1{\mu}g$of noradrenaline, but not $0.5{\mu}g$, significantly alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating effect of noradrenaline or SHG disappeared when the two compounds were administrated in equal concentrations. A significant difference (P < 0.01 in the acetone and P < 0.05 in the heat) was observed in the groups under equal doses of the two compounds, with a lower effectiveness of the combination therapy. Conclusions: Our findings suggest that the simultaneous administrations of noradrenaline and SHG do not result in synergistic analgesia, and combination therapy may not be a good approach to the treatment of chronic neuropathic pain syndrome.

Rhynchophylline, One of Major Constituents of Uncariae Ramulus et Uncus Enhances Pentobarbital-induced Sleep Behaviors and Rapid Eye Movement Sleep in Rodents

  • Yoo, Jae Hyeon;Ha, Tae-Woo;Hong, Jin Tae;Oh, Ki-Wan
    • Natural Product Sciences
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    • v.22 no.4
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    • pp.263-269
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    • 2016
  • Rhynchophylline (RP) is a major tetracyclic oxindole alkaloid of Uncariae Ramulus et Uncus which has been used to treat hypertension, seizures, pain and anxiety in the oriental countries. A recent report revealed that RP attenuated ischemia-induced neuronal damage and kainite-induced convulsions in animals. This study was performed to investigate whether RP enhances pentobarbital-induced sleep behaviors and modulates sleep architecture in mice. Locomotor activity was significantly inhibited by RP at 0.25 and 0.5 mg/kg, similar to 2 mg/kg diazepam (a benzodiazepine agonist) in mice. RP shortened sleep latency and increased total sleep time in a dose-dependent manner when administrated with pentobarbital (42 mg/kg, i.p.). RP also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). On the other hand, RP (0.25 mg/kg, p.o.) itself significantly inhibited sleep-wake cycles, prolonged total sleep time, and rapid eye movement in rats. In addition, RP also increased chloride influx in the primary cultured hypothalamic neuronal cells. In addition, we found that glutamic acid decarboxylase ($GAD_{65/67}$) was activated by RP. In conclusion, RP augments pentobarbital-induced sleeping behaviors, and can be a candidate for treating insomnia.

Somatostatin Receptors 3, 4 and 5 Play Important Roles in Gallbladder Cancer

  • Guo, Run-Sheng;Shi, Pei-Dong;Zhou, Jie;Chen, Yue-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4071-4075
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    • 2013
  • Expression changes of somatostatin receptor subtypes (SSTRs) including SSTR1, SSTR2, SSTR3, SSTR4 and SSTR5 in the development of gallbladder cancer were assessed with attention to relationships with clinical pathological characteristics. SSTRs in 29 gallbladder cancer and 25 normal gallbladder tissue specimens were examined by immunohistochemical staining. Differences between SSTRs expressions and clinical pathological parameters were analyzed by chi-square test. The five subtypes of SSTR were all expressed in gallbladder cancer tissues and SSTR3 presented the highest expression. SSTR5 expression was increased significantly in gallbladder cancer (P<0.05) compared with that in normal gallbladder tissue. SSTR3 expression in highly and moderately differentiated gallbladder cancer was significantly higher than that in poorly differentiated lesions (P<0.05). SSTR4 expression was lower in gallbladder cancer with lymph node metastasis than that in gallbladder cancer without lymph node metastasis (P<0.05). Therfore, these results indicated that SSRT5, SSTR3 and SSTR4 may play important roles in the formation and development of gallbladder cancer.

Role of Soluble Adiponectin Receptor 2 in Non-Alcoholic Fatty Liver Disease in Children

  • Aksoy, Gulsah Kaya;Artan, Reha;Aksoy, Cihat;Ozdem, Sebahat;Atalay, Atike;Yilmaz, Aygen
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.22 no.5
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    • pp.470-478
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    • 2019
  • Purpose: The incidence of non-alcoholic fatty liver disease (NAFLD) in children is gradually increasing. The aim of this study was to investigate the use of serum adiponectin and soluble adiponectin receptor 2 (soluble Adipo R2) levels for the diagnosis of fatty liver disease in obese and overweight children. Methods: The study included 51 obese and overweight children between the ages of 6 and 18 years diagnosed with NAFLD using ultrasonography and 20 children without fatty liver disease. Patients whose alanine transaminase level was two times higher than normal (${\geq}80U/L$) were included in the non-alcoholic steatohepatitis (NASH) group. Results: NASH was observed in 11 (21.6%) of the patients with NAFLD. The incidence of obesity was higher in patients with NASH (80% and 45%, p=0.021). While the adiponectin levels were similar in patients with NAFLD and those without, they were below the normal level in the whole study group. Adiponectin and soluble Adipo R2 levels of patients with NASH were lower than those in patients without NASH; however, this difference was not statistically significant (p=0.064 and p=0.463). Soluble Adipo R2 levels in obese patients with NAFLD were higher than those in obese children without NAFLD (p<0.001). Conclusion: Soluble adiponectin receptor 2 level is a noninvasive marker that can be used for the diagnosis of NAFLD in obese children.

Inositol 1,4,5-Trisphosphate-induced Increase in $Ca^{2+}-ATPase$ Activity in the Microsomes of Tracheal Epithelial Cells

  • Cho, Hyoung-Jin;Park, Sung-Shin;Kim, Young-Kee
    • The Korean Journal of Physiology
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    • v.29 no.2
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    • pp.269-277
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    • 1995
  • Membrane vesicles were prepared by differential centrifugation from epithelial cells of porcine trachea. Total activity of microsomal ATPases was measured spectrophotometrically by a coupled enzyme assay. The steady-state activity of the enzyme was $329{\pm}10$ nmol/min mg protein. Thapsigargin, a specific antagonist of intracellular $Ca^{2+}-ATPase$, inhibited about 50% of the activity, leaving $178{\pm}18\;nmol/min .mg$ protein (n=6), indicating that the $Ca^{2+}-ATPase$ is one of the major microsomal ATPases. The microsomes used in this study appeared to be tight-sealed vesicles since they showed saturation in $^{45}Ca^{2+}$ uptake experiments. Inositol 1,4,5-trisphosphate $InsP_{3}, 4\;{\mu}M$, an agonist of $InsP_{3}$-sensitive $Ca^{2+}$ release channel ($InsP_{3}$, receptor), and Ca-ionophore A23187 $(10\;{\mu}M)$ induced $^{45}Ca^{2+}$ releases of 20% and 50% of stored $^{45}Ca^{2+}$, respectively. The addition of $(10\;{\mu}M\;InsP_{3}$ also increased the microsomal ATPase activity from $282{\pm}8$ nmol/min mg protein to $334{\pm}21$ nmol/min . mg protein in the intact vesicles. Similar increase in the activity was observed by making microsomes leaky (uncoupling) using the Ca-ionophore A23187. ;$InsP_{3}-induced$ effects were blocked by either thapsigargin or heparin suggesting that: 1) the $InsP_{3}-induced$ increase in ATPase activity is mediated by microsomal $Ca^{2+}-ATPase$, and 2) dissipation of $Ca^{2+}$ gradient across the microsomal membrane is responsible for the $InsP_{3}-induced$ effect. In order to test the dependence of the $Ca^{2+}-ATPase$ activity on the activity of $InsP_{3}-induced$ the activity of ATPases was monitored in various concentrations of free $Ca^{2+}$ using $EGTA-Ca^{2+}$ buffers. The $Ca^{2+}$-dependent biphasic change is the well-known character of $InsP_{3} receptor but not of microsomal $Ca^{2+}-ATPase$ in non-excitable cells; however, the activity of microsomal ATPase appeared biphasic and a maxim진 activity of $397{\pm}36nmol/min\;.mg$ protein was obtained in the solution containing 100 nM free $Ca^{2+}$. Below or above this concentration, the activity of ATPases was lower. These results strongly support a positive correlation of microsomal $Ca^{2+}-ATPase$ to the $InsP_{3}$ receptors in epithelial microsomes.

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