• 제목/요약/키워드: $P_{2Y}$ receptor

검색결과 1,283건 처리시간 0.038초

한국인 정신분열증 환자와 도파민 $D_3$ 수용체 유전자의 연합 (Lack of Association Between the Dopamine $D_3$ Receptor Gene and Korean Schizophrenic Patients)

  • 한문균;이민수;이대희
    • 생물정신의학
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    • 제2권2호
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    • pp.237-247
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    • 1995
  • 도파민 $D_3$ 수용체 유전자와 정신분열증 병인과의 연관성을 밝히고자 본 연구에서는 한국에서의 정신분열증환자 66명과 정상대조군 76명에서 다형성의 분포를 PCR을 이용하여 환자대조연구 방법으로 조사하였다. 정신분열증환자에서 대립유전자 1의 빈도는 0.66이었고, 정상 대조군에서는 0.76이었다. 즉, 두군간에 대립유전자 1의 빈도에는 유의한 차이가 없었고, 양성 및 음성 증상군 척도평가에 의한 정신분열증의 양성아형과 음성아형간에도 유의한 차이가 없었다. 정신분열증 환지에서는 전체 66명중 동형 접합체가 43명으로 65.1%. 이형 접합체는 23명으로 34.9%였다. 정상 대조군에서는 전체 76명중 동형접합체가 54명으로 71.1%. 이형접합체는 28.9%였다. 이러한 결과는 이전의 정신분열증과 도파민 $D_3$ 수용체 유전자간의 연관관계를 연구한 외국의 연구결과와 일치하며 도파민 $D_3$ 수용체 유전자가 정신분열증 병인의 원인일 것이라는 가설을 뒷받침하지는 못하였다.

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Mouse뇌에서 Opioid 수용체 결합력에 미치는 인삼의 영향 (Effect of Total Ginseng Saponin on the Opioid Receptor Binding in Mouse Brain)

  • Kim, Soo-Kyung;Lee, Seong-Ryong;Park, Chang-Gyo
    • Journal of Ginseng Research
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    • 제19권3호
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    • pp.219-224
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    • 1995
  • The modulatory effects of total ginseng saponin (TGS) on the 1, 6, and opioid receptor binding in morphine tolerance and dependence were examined in this study. The specific [$^{3}H$]DAGO ([D-$Ala^2$, N-$Mephe^4$, $Glyco^4$] enkephalin) binding was significantly increased in chronic morphine (10 mg/kg, i.p.) treated mouse striatum. The specific [$^{3}H$]DPDPE ([D-$Pen^2$, D-$Pen^5$] enkephalin) binding was ignificantly increased following morphine treatment in the mouse striatum and cortex. Also, an apparent decrease in the affinity of [$^{3}H$]DPN (diprenorphine) was observed after chronic morphine treatment in mouse striatum and cortex. 7GS produced a sleight increase of specific [$^{3}H$]DAGO, [$^{3}H$]DPDPE binding and a significant increase of specific [$^{3}H$]DPN binding in the mouse brain striatum. In cortex, TGS produced an inhibition of specific [$^{3}H$]DAGO and [$^{3}H$]DPDPE binding and increase of the specific [$^{3}H$]DPN binding. The prolonged administration of TGS (25, 50, 100, and 150 mg/kg, i.p., 3 wks) produced an inhibition of increased [$^{3}H$]DAGO specific binding following morphine without significant changes in the agonist binding to and receptors in mouse striatum and cortex. These contracted alterations in $\mu$, $\gamma$ and $\kappa$ opiate receptor binding were dependent in TGS dogs and brain sites.

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Activation of Estrogen Receptor by Bavachin from Psoralea corylifolia

  • Park, Joon-Woo;Kim, Do-Hee;Ahn, Hye-Na;Song, Yun-Seon;Lee, Young-Joo;Ryu, Jae-Ha
    • Biomolecules & Therapeutics
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    • 제20권2호
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    • pp.183-188
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    • 2012
  • In this study, we examined the estrogenic activity of bavachin, a component of Psoralea corylifolia that has been used as a traditional medicine in Asia. Bavachin was purified from ethanolic extract of Psoralea corylifolia and characterized its estrogenic activity by ligand binding, reporter gene activation, and endogenous estrogen receptor (ER) target gene regulation. Bavachin showed ER ligand binding activity in competitive displacement of [$^3H$] $E_2$ from recombinant ER. The estrogenic activity of bavachin was characterized in a transient transfection system using $ER{\alpha}$ or $ER{\beta}$ and estrogen-responsive luciferase plasmids in CV-1 cells with an $EC_{50}$ of 320 nM and 680 nM, respectively. Bavachin increased the mRNA levels of estrogen-responsive genes such as pS2 and PR, and decreased the protein level of $ER{\alpha}$ by proteasomal pathway. However, bavachin failed to activate the androgen receptor in CV-1 cells transiently transfected with the corresponding receptor and hormone responsive reporter plasmid. These data indicate that bavachin acts as a weak phytoestrogen by binding and activating the ER.

Plant Inositol Signaling - Biochemical Study of Phospholipase C and D-myo-inositol -1,4,5-trisphosphate receptor

  • Martinec, Jan;Feltl, Tomas;Nokhrina, Katerina;Zazimalova, Eva;Machackova, Ivana
    • 식물조직배양학회지
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    • 제27권5호
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    • pp.375-377
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    • 2000
  • It is now generally accepted that a phosphoinositide cycle is involved in the transduction of a variety of signals in plant cells. In animal cells, the hydrolysis of phosphatidyl-4,5-bisphosphate catalysed by phosphatidylinositol - specific phospholipase C yields to D-myo-inositol - 1,4,5-trisphosphate and diacylglycerol, which are well known second messengers. The binding of InsP$_3$to a receptor located on the endoplasmic reticulum triggers a calcium release from the endoplasmic reticulum. We have detected and partially characterised key components of phosphoinositide signaling. First, tobacco microsomal fraction and plasma membrane PI-PLC. Consecutively, using a radioligand binding assay we have identified a $Ca^{2+}$ -dependent high affinity InsP$_3$binding site in microsomal membrane fraction vesicle preparation and then we have measured inositol-1,4,5-trisphosphate induced calcium release from tobacco microsomal fraction. These findings suggest that phosphoinositide signaling system is present and operates in the tobacco suspension culture.e.

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In vivo Pharmacological Evaluation of Newly Synthesized Nonpeptidic $AT_1$ Receptor Antagonists in Rats

  • Lee, Byung-Ho;Shin, Hwa-Sup
    • Archives of Pharmacal Research
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    • 제17권4호
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    • pp.263-268
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    • 1994
  • This study was conducted to characterize the in vivo pharmacology of KR-30988, KR-30992 and losartan, new AT antagonists, given as i.v. cumulative doses, in two antimal models of high renin, conscious renal artery-ligated hypertensinve rats (RHRs) and nomotensive rats anesthetized with urethane (90 mg/kg, i.p.) and .alpha.-chloralose (90 mg/kg, i.p.), with a special emphasis on the phamacological characterization of the latter model. In conscious RHRs, KR-30988, KR-30992, losartan and captopril caused a dose-dependent decrease in blood pressure, their relative potencise ($ED_{20}$) being 0.057, 0.028, 0164 and 0.018 mg/kg, i.v., repectively. In anesthetized rats, 2 hours after anesthesia, plasma renin activity was increased from 7.31 tp 34.07 ng/ml/h, the level approximately 1.5 times greater than the highest level in RHRs. In anesthtized rats, the $ED_{20}$s for all four compounds were 0.004 mg/kg i.v., respectively. By comparison, $ED_{20}$sfrom anesthetized rats were 4 to 5 times smaller than those from conscious RHRs, with a good correlation (.gamma. = 0.999) noted between thetized rats to the hypotensive activity of the compounds and the same order of potencies intwo models. These results suggest that, in addition to PHRs, the normotensive rats anesthetized as above can serve as a suitable model for the rapid phamacological evaluation of $AT_1$ receptor antagonists.

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Dopamine이 흰쥐 자궁의 자발적 수축에 미치는 영향 (Role of Dopamine upon Spontaneous Contraction of Isolated Rat Uterus in Diestrus State)

  • 박형진;심여림;조양혁
    • The Korean Journal of Physiology
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    • 제17권2호
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    • pp.103-107
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    • 1983
  • This experiment was undertaken to see whether dopamine has any effect on a uterine function and whether the uterus has a dopamine receptor. We used 14 female rats in the diestrus state which was identified by a vaginal smear. Under ether anesthesia, 3 pieces(1 cm length) from each side of the uterus were dissected out and mounted in 3 tissue chambers (4 cm diameter, 10 cm height) that contained Krebs-Ringer solution. The solution was continuously aerated with 95% $O_2$ containing 5% $CO_2$ and kept $37^{\circ}C$ consistantly during the whole experimental period. The spontaneous contractile activity of the isolated uterus was recorded using a force transducer. After a recovery period of 15 min in the chamber, the following experiments were carried out. In 7 rats, each piece of the uterus was received dopamine at concentrations of $10^{-4}$, $10^{-5}$ or $10^{-6}\;M$ for 10 min and then followed by domperidone at a concentration of $10^{-5}\;M$. In another 7 rats, each piece was received domperidone, a specific peripheral dopamine receptor antagonist, was administered at a concentration of $10^{-5}\;M$ for 5 min prior to dopamine at concentrations of $10^{-4}$, $10^{-5}$, or $10^{-6}\;M$. Dopamine inhibited the spontaneous uterine contraction dose-dependently (r=0.99, p<.01). The inhibited contractility by dopomine was significantly (P<.05) resumed by post-treatment of domperidone. Pre-treatment of domperidone also blocked significantly(p<.05) the inhibitory effect of dopamine. It is concluded from these results that dopamine has inhibitory role upon the spontaneous uterine contraction of the rat in the diestrus state and domperidone antagonized the inhibitory effect of dopamine. These results suggest strongly that dopamine may exert the inhibitory effect via the dopamine receptor in the rat uterus.

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제주재래돼지와 듀록 참조축군에서 Melanocortin 4 Receptor (MC4R) 유전자형과 지방산 조성간의 관련성 분석 (Association of Melanocortin 4 Receptor (MC4R) Genotypes with Fatty Acid Compositions in an Intercross Population between Duroc and Jeju Native Pigs)

  • 강용준;김상금;김수연;신문철;우제훈;김남영;신상민;최재영;유지현;박남건;양병철;조인철
    • 생명과학회지
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    • 제30권1호
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    • pp.58-63
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    • 2020
  • 본 연구에서는 제주재래돼지와 듀록 품종 사이에서 생산된 F2 참조축군에서 melanocortin-4-receptor (MC4R) 유전자형과 지방산 조성간의 관련성을 연구하였다. 전체 290 여두의 F2 자손을 이용하여 14개의 지방산 조성을 측정하였다. Taq I PCR-RFLP 방법을 이용하여 MC4R c.1426A>G (p.Asp298Asn)의 단일염기다형성(single nucleotide polymorphism, SNP)을 확인하였다. MC4R 세 가지 유전자형(AA, AB, BB)이 모두 발견되었고, 그 빈도는 각각 0.299, 0.542, 0.159로 확인되었다. AA 유전자형을 가진 개체에서 palmitic acid (C16:0, p<0.05), stearic acid (C18:0, p<0.01), eicosenoic acid (C20:1n9, p<0.05), saturated fatty acid (SFA, p<0.01) 함량이 GG 유전자형을 가진 개체보다 더 높은 것으로 확인되었다. 반면에 GG 유전자형을 가진 개체는 linoleic acid (C18:2n6, p<0.001), linolenic acid (C18:3n3, p<0.001), linolenic acid (C18:3n6, p<0.001), arachidonic acid (C20:4n6, p<0.001)과 같은 불포화지방산(unsaturated fatty acid) 함량이 AA 유전자형을 가진 개체보다 더 높은 것을 확인하였다. 제주재래돼지와 듀록 품종 사이에서 생산된 F2 참조축군에서 MC4R GG 유전자형이 포화지방산은 낮추고, 불포화지방산은 높이는 것으로 확인되었다. 본 연구 결과 MC4R의 유전적 다형성이 듀록과 제주재래돼지 교배 프로그램에서 육질 향상과, 고기내의 지방산 함량을 조절할 수 있는 유전적 표지 인자로 활용될 수 있을 것이라 사료된다.

한국적 의학 기준에 근거한 고혈압환자의 Angiotensin II Receptor Blockers와 Calcium Channel Blockers의 약물 평가 (Evaluation of Therapeutic Differences of Angiotensin II Receptor Blockers and Calcium Channel Blockers Among Hypertensive Patients Classified by Oriental Traditional Way)

  • 이옥상;천영주;예경남;윤희영;김정태;이윤정;임성실
    • 약학회지
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    • 제58권2호
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    • pp.141-149
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    • 2014
  • Background: Oriental lifestyle for treating diseases has been developed and well-accepted for a long time among Koreans. Sasang Constitution theory, originated from Korean traditional medicine, suggests that medication treatment should be differentiated by each patient's body classification (So-yang [SY], So-eum [SE], Tae-yang [TY], and Tae-eum [TE]), in contrary to western medicine's theory that medication should be applied equally by disease indication without such classification. However, the pharmacotherapeutic outcomes of these theories have not been compared to date. In this study, we aimed to compare the two theories by evaluating blood pressure (BP), which is lowered as a therapeutic outcome, among hypertensive patients taking angiotensin II receptor blockers (ARBs) or calcium channel blockers (CCBs), two most commonly used antihypertensive classes in Korea. Methods: From April 2006 to June 2012, we retrospectively collected data on hypertensive patients with Sasang Constitution classification at Kyunghee University Hospital at Gangdong, one of the East-West collaborative medical centers in Korea. We collected information on age, gender, underlying diseases, antihypertensive drugs (ARB, CCB, ARB+CCB), and BP by reviewing the electronic medical records. We excluded patients with missing blood pressure at baseline or follow-up, or those who had a change in their antihypertensive drug class during follow-up. Results: We selected a total of 573 patients (SY: 165, SE: 158, TY: 0, TE: 250). Baseline BPs were on average 139.0/82.0 mmHg for SY, 137.8/78.5 mmHg for SE, and 138.7/79.2 mmHg for TE. In all three groups, CCBs were the most prescribed, followed by combination therapy with ARB+CCB, then ARBs. BP reduction after 1 month of initial medication was significantly different among the drug classes, but not in Sasang constitutional classification (ARB [SY: -12.4/-4.7, SE: -12.3/-2.5, TE: -8.6/-1.8], CCB [SY: -12.3/-5.4, SE: -13.0/-2.3, TE: -10.8/-6.0], ARB+CCB [SY: -15.6/-6.7, SE: -18.4/-8.1, TE: -20.2/-6.7], drug [$P{\leq}0.05$/P>0.05], constitutional type [P>0.05/P>0.05]). Conclusion: We observed significant differences in reduction of blood pressure by classes of drugs (ARB+CCB>CCB>ARB) but not by Sasang constitutional classification. Therefore, current approach of antihypertensive pharmacotherapy assisted by Western medicine is appropriate for treatment of hypertension. However, further larger scale or prospective studies are required in order to confirm these results.

Differential Effects of Anti-IL-1R Accessory Protein Antibodies on IL-1α or IL-1β-induced Production of PGE2 and IL-6 from 3T3-L1 Cells

  • Yoon, Do-Young;Dinarello, Charles A.
    • BMB Reports
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    • 제40권4호
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    • pp.562-570
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    • 2007
  • Soluble or cell-bound IL-1 receptor accessory protein (IL-1RAcP) does not bind IL-1 but rather forms a complex with IL-1 and IL-1 receptor type I (IL-1RI) resulting in signal transduction. Synthetic peptides to various regions in the Ig-like domains of IL-1RAcP were used to produce antibodies and these antibodies were affinity-purified using the respective antigens. An anti-peptide-4 antibody which targets domain III inhibited 70% of IL-$1\beta$-induced productions of IL-6 and PGE2 from 3T3-L1 cells. Anti-peptide-2 or 3 also inhibited IL-1-induced IL-6 production by 30%. However, antipeptide-1 which is directed against domain I had no effect. The antibody was more effective against IL-$1\beta$ compared to IL-$1\alpha$. IL-1-induced IL-6 production was augmented by coincubation with PGE2. The COX inhibitor ibuprofen blocked IL-1-induced IL-6 and PGE2 production. These results confirm that IL-1RAcP is essential for IL-1 signaling and that increased production of IL-6 by IL-1 needs the co-induction of PGE2. However, the effect of PGE2 is independent of expressions of IL-1RI and IL-1RAcP. Our data suggest that domain III of IL-1RAcP may be involved in the formation or stabilization of the IL-1RI/IL-1 complex by binding to epitopes on domain III of the IL-1RI created following IL-1 binding to the IL-1RI.

N-methyl-D-aspartate glutamate 수용체 길항제 memantine의 투여가 C57BL/6형 생쥐의 알코올 섭취량에 미치는 영향 (Effect of N-Methyl-D-Aspartate Glutamate Receptor Antagonist, Memantine, on Alcohol Intake in C57BL/6 Mice)

  • 김현경;김성곤;김지훈;신수미;이상신;배소현;김호찬
    • 생명과학회지
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    • 제19권4호
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    • pp.532-537
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    • 2009
  • 알코올 의존과 N-methyl-D-aspartate (NMDA) 수용체와 밀접한 관계가 있을 수 있다는 연구들이 있는데, 즉 NMDA 수용체가 알코올의 금단, 내성의 발생과 관련이 있다는 연구 결과들이다. 그러나 NMDA 수용체 길항제가 알코올 의존의 재발 예방에 효과가 있을 것이라는 것에 대해서는 아직 논란이 되고 있다. 본 연구는 유전적으로 알코올을 선호하는 C57BL/6형 생쥐를 이용하여 유한접근법으로 NMDA 수용체 길항제인 memantine을 5, 25, 50 mg/kg으로 각각 투여하였을 때 알코올 섭취량에 미치는 영향을 알아보고자 하였다. 알코올 의존화된 C57BL/6형 수컷 생쥐를 5군으로 나눈 뒤, 12일간 각 군에 vehicle, naltrexone 1.0 mg/kg, memantine 5, 25, 50 mg/kg으로 각각 투여하면서 알코올의 섭취량, 물 섭취량, 사료 섭취량 및 체중을 조사하였다. 본 연구의 결과, 2시간 알코올 섭취량의 12일간 변화에 대해 vehicle 투여군과 naltrexone, memantine 5, 25, 50 mg/kg 투여군 각각의 군을 repeated measure ANOVA를 이용하여 비교하였을 때, naltrexone (df=4, F=11.827, p<0.01), memantine 5 mg/kg (df=4, F=7.999, p<0.01), memantine 25 mg/kg (df=4, F=6.199, p<0.05) 및 memantine 50 mg/kg (df=4, F=10.522, p<0.01) 투여군에서 각각 유의한 군과 일수의 상호작용을 보였다. 그러나 22시간 물 섭취량, 24시간 사료섭취량 및 체중의 12일간 변화에 대해서는 vehicle 투여군과 memantine 투여군 3군 각각에서 유의한 상호작용이 없었다. 한편, vehicle 투여군과 naltrexone 투여군 간에는 체중의 변화에서 유의한 군과 일수의 상호작용을 보였고, 22시간 물 섭취량 및 24시간 사료 섭취량에서는 유의한 상호 작용이 없었다. 이상의 결과는 NMDA 수용체 길항제인 memantine을 생쥐에게 투여하였을 때 알코올 섭취량에 영향을 줄 수 있다는 것을 의미한다. 이는 앞으로 부작용은 적으면서 치료 효과는 우수한 알코올 의존 재발 예방 치료제 개발의 가능성을 제안하고 있다.