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Pro-apoptotic Effects of Platycodin D Isolated from Platycodon grandiflorum in Human Leukemia Cells (도라지 유래 사포닌 platycodin D에 의한 인체 백혈병세포의 apoptosis 유도)

  • Park, Sang Eun;Lee, Su Young;Shin, Dong Yeok;Jeong, Jin-Woo;Jin, Myung Ho;Park, Seon Young;Chung, Yoon Ho;Hwang, Hye Jin;Hong, Sang Hoon;Choi, Yung Hyun
    • Journal of Life Science
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    • v.23 no.3
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    • pp.389-398
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    • 2013
  • Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.

The Influence of 5-Fluorouracil Administration Mode on the Expression of Phospholipase C and Ras Oncoprotein Associated with Regeneration of Rat Intestinal Mucosa Following Radiation (방사선 조사후 백서 공장 점막의 재생과정에서 5-fluorouracil 투여가 phospholipsse C 와 ras 암유전자단백의 발현에 미치는 영향)

  • Park Kyung Ran;Lee Chung Sik;Kim Sung Sook;Lee Young Han;Ryu Sung Ho;Suh Pann-Ghill
    • Radiation Oncology Journal
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    • v.12 no.3
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    • pp.271-284
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    • 1994
  • Purpose : Phospholipase C(PLC) isozymes play significant roles in transmembrane signal transduction. PLC-${\gamma}1$ acts as the intracellular effector in signal transduction for cellular proliferation and differentiation. Ras oncoprotein is also involved in cell growth. We determined the biological significance of PLC and ras oncoprotein in regeneration following radiation and the effect of different modes of administration of 5-FU. Materials and Methods : To determine the effect of the administration mode of 5-FU on the regeneration of intestinal mucosa of rats following radiation, we compared the expression of PLC and ras oncoprotein in six groups. Group I had no treatment. Group II received radiation(8 Gy) only. Group III received radiation(8 Gy) and 5-FU(150mg/kg) continuous intravenous (iv) infusion for 12 hours. Group IV received radiation(8 Gy) and 5-FU(750mg/kg) iv bolus injection. Group V received only 5-FU(150mg/kg) continuous iv infusion for 12 hours, Group VI received only 5-FU (150mg/kg) iv bolus injection. Through immunoblotting and immunohistochemistry, we examined the expression of PLC and ras oncoprotein in rat jejunum at 96 hours after radiation or 5-FU administration and at 120 hours after radiation and 5-FU adminstration. We also investigated the histological findings using hematoxylin and eosin stain. Results : In the immunohistochemistry study, PLC-${\gamma}1$ expression was the highest in group III followed by groups II and VI in that order and was weakly positive in groups V and VI. PLC-${\gamma}1$ was hardly detected in the control group. The expression of ras oncoprotein was the same as the PLC-${\gamma}1$ expression for all groups. These results were confirmed by the histological findings regarding the mucosal regeneration. In the immunoblotting analysis, PLC-${\gamma}1$ expression was the highest in group III followed by group IV and II in that order. This difference between the immunoblotting and immunohistochemistry study was due to the high expression of PLC-${\gamma}1$ on the damaged surface epithelium rather than to its expression in the regeneration region as observed in the immunohistochemistry study for group IV. The expression of PLC-${\delta}1$ was positive only in group V and VI, which received both radiation and 5-FU, and the expression of PLC-${\beta}1$ was negligible for all groups. Conclusion : These results suggest that PLC-${\gamma}1$ mediated signal transduetion and ras oncoprotein may have a significant role in mucosal regeneration after radiation, and that continuous iv infusion of 5-FU may induce active regeneration in intestinal mucosa following radiation. In addition, the expression of PLC-${\delta}1$ in combined group of radiation and 5-FU implies that PLC-${\delta}1$ may be involved in signal transduction mediated by concerted action between radiation and 5-FU.

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Effect of Natural Plant Mixtures on Behavioral Profiles and Antioxidants Status in SD Rats (자생식물 혼합 추출물이 SD 흰쥐에서의 행동양상 및 항산화 체계에 미치는 영향)

  • Seo, Bo-Young;Kim, Min-Jung;Kim, Hyun-Su;Park, Hae-Ryong;Lee, Seung-Cheol;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.9
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    • pp.1208-1214
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    • 2011
  • Caffeine, a psychoactive stimulant, has been implicated in the modulation of learning and memory functions due to its action as a non-selective adenosine receptors antagonist. On the contrary, some side effects of caffeine have been reported, such as an increased energy loss and metabolic rate, decrease DNA synthesis in the spleen, and increased oxidative damage to exerted on LDL particles. Therefore, the aim of this study was to develop a safe stimulant from natural plants mixture (Aralia elata, Acori graminei Rhizoma, Chrysanthemum, Dandleion, Guarana, Shepherd's purse) that can be used as a substitute for caffeine. Thirty SD rats were divided into three groups; control group, caffeine group (15.0 mg/kg, i.p.), and natural plants mixture group (NP, 1 mL/kg, p.o.). The effect of NP extract on stimulant activity was evaluated with open-field test (OFT) and plus maze test for measurement of behavioral profiles. Plasma lipid profiles, lipid peroxidation in LDL (conjugated dienes), total antioxidant capacity (TRAP) and DNA damage in white blood, liver, and brain cells were measured. In the OFT, immobility time was increased significantly by acute (once) and chronic (3 weeks) supplementation of NP and showed a similar effect to caffeine treatment. Three weeks of caffeine treatment caused plasma lipid peroxidation and DNA damage in liver cells, whereas there were no changes in the NP group. NP group showed a higher plasma HDL cholesterol concentration compared to the caffeine group. The results indicate that the natural plants mixture had a stimulant effect without inducing oxidative stress.

Development of Health Promotion Program through IUHPE - Possibilities of collaboration in East Asia - (IUHPE를 통한 건강 증진 프로그램의 발달-동아시아권의 공동연구의 가능성-)

  • Moriyama, Masaki
    • Proceedings of The Korean Society of Health Promotion Conference
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    • 2004.10a
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    • pp.1-16
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    • 2004
  • This paper considers the possibilities of health promotion from the following perspectives; (1) IUHPE, (2) socio-cultural similarities, (3) action research, and (4) learning from our past. 1. The IUHPE values decentralized activities through regions, and countries such as Japan, Korea, Hong Kong, Taiwan and China belong to NPWP region. Since IUHPE World Conference was held in Japan in 1995, Japan used to occupy more than 60% of NPWP membership. After 2001, membership is increasing rapidly in Chinese speaking sub-region. The transnational collaboration is still in its beginning phase. 2. Confucianism is one of key points. Confucian tradition should not be seen only as obstacles but as advantages to seek a form of health promotion more acceptable in East Asia. 3. Within the new public health framework, people are expected to create and live their health. However, especially in Japan, the tendency of 'lacking of face-to-face explicit interactions' is still common at health-promotion settings as well as academic settings. Therefore, the author tried participatory approaches such as asking WlFY (interactive questions designed for subjects to review their daily life and environment) and as introducing round table interactions. So far, majority of participants welcome new trials. 4. The following social phenomena are comparatively discussed after Japanese invasion and occupation of Korea ended in 1945; ·status of oriental medicine, ·separation of dispensary services, and ·health promotion specialist as a national license. In contrast to Japanese' tendency of maintaining the status quo and postponing of substantial social change, trend toward rapid and dynamic social changes are more commonly observed in Korea. Although all of above possibilities are still in their beginning stages, they are going to offer interesting directions waiting for further challenges and accompanying researches.

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Knowledge and Attitude toward Restaurant-Related Sanitation of New Restaurateurs (일반음식점 신규영업주의 위생관리지식 및 위생행정에 대한 태도)

  • Kim, Seun-Taek;Park, Jae-Yong;Kam, Sin;Han, Chang-Hyun
    • Korean Journal of Health Education and Promotion
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    • v.15 no.1
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    • pp.79-95
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    • 1998
  • The purpose of this study was to investigate the sanitation affairs of general restaurants. The questionnaire survey on the attitude and knowledge toward sanitation, the attitude for sanitary administration and the sanitary education was conducted against new 600 restaurateurs who were educated from June 20 to July 11, 1996, at the administration hall's division of Kyungsangbook-do in charge of food industry that offered regular sanitary education to new restaurateurs annually. And the visit survey on sanitary practice was also conducted over 93 restaurateurs who obtained the commercial license for food service business. The findings from the survey were as follows; In regard to food sanitation, some 87.1 to 88.3% got the right knowledge about the reason and precaution of food poisoning, food's frozen or cold-storage, and the disposal of products after expiration of validity term. But it was about 20.8% to 50.0% who knew right about major precaution, storage temperature in refrigerator, fermented milk product's storage temperature and validity term. There was therefore a necessity for education in food sanitation. 38.2% of the subjects placed an emphasis on sanitary storage of foodstuffs as the most important thing in sanitary management. 33.8% emphasized cooking sanitation. The environmental sanitation was counted as the most important thing by 19.2%, and personal sanitation of worker was counted by 8.8%. There was differences in what they thought the most important thing was, according to the respondent's educational level and cooker. 86.6% replied it necessary to improve the sanitary level. The respondents who were younger or had better educational level emphasized more the need for it. Concerning health examination, 90.2% replied it necessary. 81.4% answered the reason was because there was a potentiality Quests might be infected with contagious disease. 78.5% pointed the need for sanitary education, but respondents with higher educational level less emphasized its needs. As the reason for poor sanitation, restaurateur's poor awareness about it was most frequently pointed out, by 46.9%. Cooking sanitation was most frequently counted, by 38.5%, as the first thing to be improved. As the most critical point in sanitary education, 34.5% indicated food's sanitary Quality control 30.9% mentioned sanitary treatment of kitchen facilities and peripheral environment, and 27.1% emphasized the summary of the general food sanitation. 77.7% answered to correct immediately in case of violating the Food Hygiene Law, and 12.0% replied to correct in the same case if they would get the order from public official or administrative action would be taken. Respondents with higher educational level answered more to correct immediately. What they wanted the government office to do toward sanitary improvement was a fund aid an facilities and management which was pointed out by 38.9%, a periodical sanitary education by 26.3% and a on-the-spot guidance of sanitary officials by 22.3%. In view of the food service business's sanitary practice, the rate of wearing a sanitary clothes was 32.9% in city and 35.0% in county. The rate of hand-washing without soap or non-washing at cooking was 73.9%, 85%, respectively. The rate of personnel sanitation was 34.2% in city and 50.0% in county. These things indicated the sanitation was not well practiced. To improve the poor sanitary conditions of the food service businesses, it is recommended to offer institutional backing and financial aid from administrative office, and encourage restaurateurs to take pride in their job. and conduct the sanitary education effectively by sanitary education institution.

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Insecticidal Activity of Cinnamon Essential Oils, Constituents, and (E)-Cinnamaldehyde Analogues against Metcalfa pruinosa Say (Hemiptera: Flatidae) Nymphs and Adults (미국선녀벌레(Metcalfa pruinosa Say)에 대한 계피 정유 유래 물질의 살충 활성)

  • Kim, Jun-Ran;Jeong, In-Hong;Lee, Young Su;Lee, Sang-Guei
    • Korean journal of applied entomology
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    • v.54 no.4
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    • pp.375-382
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    • 2015
  • The insecticidal activity of the constituents of cinnamon essential oils and structurally related compounds against both the nymphs and adults of the citrus flatid planthopper Metcalfa pruinosa was examined using a direct-contact application. The toxicity of the cinnamon oil constituents and 21 (E)-cinnamaldehyde related compounds regarding the nymphs of M. pruinosa was evaluated using a leaf-dipping bioassay. Based on 24 h $LC_{50}$ values, hydro-cinnamic acid ($1.55mg/cm^2$) is the most toxic compound, followed by geranic acid ($1.59mg/cm^2$). The $LC_{50}$ values of 11 of the compounds including cinnamaldehyde are between $1.60mg/cm^2$ and $4.94mg/cm^2$. Low toxicities and no toxicity were observed with the other 15 ($5.24mg/cm^2$ to $13.47mg/cm^2$) and two compounds, respectively. Also, the toxicities of the cinnamon oil constituents and 21 cinnamaldehyde related compounds regarding the M. pruinosa adults were evaluated using a direct-spray method. The toxicity of eugenol (10.81 mg) is the most toxic compound for the adults of M. pruinosa, followed by geranic acid (30.68 mg). The $LC_{50}$ values of nine of the compounds including cinnamaldehyde are between 59.16 mg and 96.70 mg. Low toxicities and no toxicity were observed with the other 15 (105.44 mg to 255.76 mg) and three compounds, respectively. The spray formulations that comprise cinnamon bark and cinnamon green leaf oils resulted in 82.3% and 82.9% mortalities, respectively, toward the M. pruinosa adults in a ginseng field. Global efforts to reduce the level of highly toxic synthetic insecticides in agricultural environments justify further studies on cinnamon oils to ascertain whether the corresponding active principles can act as insecticides, when they are applied as a direct spray with contact action, for the control of M. pruinosa populations.

Microarray Analysis of Gene Expression in Rat Glioma after Ethanol Treatment (에탄올 처리에 의한 흰쥐 신경아교종(Glioma) 세포에서의 유전자 발현 - DNA 칩을 이용한 분석 -)

  • Lee, So Hee;Oh, Dong-Yul;Han, Jin-Hee;Choi, Ihn-Geun;Jeon, Yang-Whan;Lee, Joon-Noh;Lee, Tae Kyung;Jeong, Jong-Hyun;Jung, Kyung Hwa;Chai, Young-Gyu
    • Korean Journal of Biological Psychiatry
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    • v.14 no.2
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    • pp.115-121
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    • 2007
  • Objetives : Identification of target genes for ethanol in neurons is important for understanding its molecular and cellular mechanism of action and the neuropathological changes seen in alcoholics. The purpose of this study is to identify of altered gene expression after acute treatmet of ethanol in rat gliom cells. Methods : We used high density cDNA microarray chip to measure the expression patterns of multiple genes in cultured rat glioma cells. DNA microarrays allow for the simultaneous measurement of the expression of several hundreds of genes. Results : After comparing hybridized signals between control and ethanol treated groups, we found that treatment with ethanol increased the expression of 15 genes and decreased the expression of 12 genes. Upregulated genes included Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA bindning protein 2. Downregulated genes included diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome. Conclusion : The gene changes noted were those related to the regulation of transcription, signal transduction, second messenger systems. modulation of ischemic brain injury, and neurodengeneration. Although some of the genes were previously known to be ethanol responsive, we have for the most part identified novel genes involved in the brain response to ethanol.

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EFFECTS OF SUBINHIBITORY CONCENTRATIONS OF ANTIMICROBIAL AGENTS ON CELL SURFACE PROPERTIES AND VIRULENCE FACTORS OF MUTANS STREPTOCOCCI (아저해농도(亞沮害濃度)의 항균물질이 mutans streptococci의 세포표면성질과 독력인자에 미치는 영향)

  • Kim, Young-Jae;Hahn, Se-Hyun;Lee, Sang-Hoon;Jang, Ki-Taeg;Kim, Chol-Chul
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.4
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    • pp.605-616
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    • 2004
  • Subinhibitory concentrations (sub-MICs) refer to concentrations below minimum inhibitory concentrations (MICs). The antimicrobial agents may be present at relatively high concentration, at least higher than bacterial MIC and thereafter be deserted off a surface and function at sub-MICs, perhaps by interfering with bacterial metabolism. Consequently, the aim of this study was to determine the effects of growth, in the presence of sub-MICs of antimicrobial agents, on the cell surface properties and virulence factors of mutans streptococci and to investigate the efficacy of a chemical approach in vitro. Streptococcus mutans Ingbritt and Streptococcus sobrinus 6715-7 were used. Eight antimicrobial agents (Sanguinaria extract;SG, Chlorhexidine digluconate;CHX, Fluoride;F, Propolis;PP, Hydrogen peroxide;HP, Triclosan;TC, Sodium dodecyl sulfate;SDS Cetylpyridinium chloride; CC) were diluted serially in broth to determine MICs and to compare the growth rate, acid production, hydrophobicity, adhesion activity to saliva coated hydroxyapatite, glucan synthesis and cellular aggregation of experiment groups (in the presence of sub-MICs) with those of control (in the absence of antimicrobial agents). Sub-MICs of antimicrobial agents affected the growth of cells, hydrophobicity, and adhesion of bacteria to saliva coated hydroxyapatite and glucan synthesis. They also resulted in a significant reduction in pH after 12 hours (p<0.05). By cells pretreated with proteinase K, either the aggregation induced by antimicrobial agents was completely inhibited or the aggregation titers were markedly increased. According to the results of the present study, each antimicrobial agent at sub-MICs could affect similar as its known action mechanism and could continually inhibit cariogenic bacteria at such concentrations. Thus, the use of these antimicrobial agents would be one of the effective methods to prevent dental caries.

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Effect of Reduced Glutathione on Non-Protein Sulfhydryl and Non-Protein Disulfide of the Mouse Liver in Vitro (Reduced Glutathione의 In Vitro 첨가(添加)가 마우스간조직(肝組織)의 내재(內在) NP-SH 및 NP-SS에 미치는 영향(影響))

  • Oh, Sang-You
    • The Korean Journal of Physiology
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    • v.7 no.2
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    • pp.9-16
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    • 1973
  • In view of the recent knowledge on the radioprotective action of reduced glutathione (GSH), the present study was designed the elucidate the effect of some concentrations of GSH on the levels of intrinsic non-protein sulfhydryl (NP-SH) and non-protein disulfide (NP-SS) of the mouse liver incubated at 4, 25 and 37C in vitro, respectively. The liver slice of the mouse was incubated at 4, 25 and 37C in the medium composed of 100 ml of Krebs-Ringer phosphate buffer (KRP) with the addition of 10, 20 and 30 mg of GSH, respectively. Measurement of NP-SH and NP-SS was made at 5, 30 and 60 min during the course of the incubation, and the results were compared with the controls which were incubated only in KRP medium, and the normal. The results thus obtained are summarized as follows: 1. When the mouse liver slice was incubated at 4C, the values of both NP-SH and NP-SS of the control and the group where 10 mg of GSH was added to the incubation medium were similar to those of the normal group, and the increase of NP-SH and NP-SS with the increased concentrations of GSH was not prominent. 2. When the liver slice was incubated in the concentrations of GSH 20 mg/100 ml KRP and GSH 30 mg/100 ml KRP at 25 C, the rate of increase of both NP-SH and NP-SS was proportional to the increase of GSH concentration. In the group where 10 mg of GSH was added to the incubation medium, the value of NP-SH and NP-SS reached the highest value at 30 min, but a tendency of decrease was observed at 60 min. 3. The rate of increase of NP-SH and NP-SS of the liver was most marked of all the group. studied when the incubation temperatuse was elevated to 37C, and the increase was proportional to the concentration of GSH and the incubation time.

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Influence of Yohimbine on the Central Dopaminergic Regulation of Renal Function (신장기능의 중추 Dopamine성 조절에 미치는 Yohimbine의 영향)

  • Kook, Young-Johng;Kim, Kyung-Keun;Cho, Kang-Seon;Min, Byung-Kap
    • The Korean Journal of Pharmacology
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    • v.22 no.2
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    • pp.79-87
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    • 1986
  • Recently it has been shown that central dopaminergic system regulates the renal function and that intracerebroventricularly (icv) administered dopamine (DA) produces antidiuresis and antinaturiuresis, resembling icv norepinephrine, and evidence has been accumulated which would suggest the involvement of adrenergic system in the DA effects. It was attempted therefore in this study to see whether the DA effect is influenced by pretreatment of yohimbine which is known as a specific ${\alpha}_2-adrenoceptor$ antagonist. Yohimbine produced, when given icv in doses of $100\;{\mu}g/kg$, marked antidiuresis and antinatriuresis along with decreases in renal perfusion and glomerular filtration. DA, in doses of $15\;{\mu}g/kg$, also produced antidiuresis and antinaturiuresis. However, after yohimbine-pretreatment DA $15\;{\mu}g/kg$ improved renal hemodynamics, and electrolyte excretion and urine flow rate transiently increased. With $150\;{\mu}g/kg$ DA, the antidiuresis was more marked in the control group. But the yohimbine-pretreated animals responded with marked diuresis and natriuresis, sodium excretion increasing more than three-fold, which lasted for 20 minutes. $K^+-excretion$, osmolar clearance as well as free-water reabsorption increased. Renal hemodynamics improved partly. Apomorphine, a DA agonist, when given icv in doses of $150\;{\mu}g/kg$, produced diuresis and naturiuresis, concomitant with increased renal hemodynamics. Yohimbine-pretreatment however did not abolish the apomorphine-induced diuresis and naturiuresis. Antidiuresis and antinatriuresis elicited by norepinephrine, $10\;{\mu}g/kg$, was not affected by yohimbine-pretreatment. These results indicate that the renal effects of icv DA is not so simple as those of norepinephrine, and the diuretic natriuretic cffect which had been masked by the hemodynamic effect becomes manifest only when the decreases in hemodynamics were removed by the pretreatment of yohimbine. It was further suggested that those DA receptors which mediate the natriuretic response to icv DA is not affected by yohimbine, whereas those receptors involved in the decrease in renal hemodvnamics are blocked by yohimbine. And the possibility of involvement of adrcnergic system in the DA action is not substantiated.

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