• Title/Summary/Keyword: $^{45}Ca$ uptake

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Inhibitory Effects of Amitriptyline, Sertraline and Chlorpromazine on the Thrombin-induced Aggregation of Platelets (Thrombin성 혈소판응집에 대한 Amitriptyline, Sertraline 및 Chlorpromazine의 억제작용)

  • Choi, Sang-Hyun;Lee, Young-Jae;Shin, Kyung-Ho;Chun, Yeon-Sook;Chun, Boe-Gwun
    • The Korean Journal of Pharmacology
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    • v.31 no.3
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    • pp.299-311
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    • 1995
  • Platelets resemble monoaminergic neurons in several respects, i.e. the uptake of 5-HT and its inhibition, the subcellular storage and release of 5-HT, and the metabolism of aromatic amines brought about by monoamine oxidase. And the 5-HT content of rabbit platelets is well known to be about 40 times higher than that of human platelets. Therefore, this study was carried out to investigate the influences of amitriptyline (AMT) and sertraline (SRT) on the aggregation, contents of signaling second messengers, and protein phosphorylations of rabbit platelets in response to thrombin, 0.25 unit/ml, comparing with those of chlorpromazine (CPZ). Thrombin-induced aggregation was inhibited by SRT $(IC50:4.37{\times}10^{-5}\;M)$, CPZ $(IC50:5.76{\times}10^{-5}\;M)$, and AMT $(IC50:1.15{\times}10^{-4}\;M)$, respectively, and the aggregation by A23187 $(1.0\;{\mu}M)$ or PMA (320 nM) was also inhibited by SRT, CPZ, and AMT. AMT, SRT, and CPZ had little affects on basal contents of platelet $TXB_2$ and $PGE_2$, but all of them inhibited the thrombin-induced increase of $TXB_2$. Thrombin did not change the platelet contents of cAMP and cGMP. CPZ, AMT, and SRT produced the slight decrease of basal cAMP content, and their effects were not affected by thrombin-treatment. But SRT and AMT moderately increased the basal cGMP content, and the cGMP content of thrombin-stimulated platelets was gradually increased by the pretreatment with SRT, AMT, and CPZ. Particularly, the SRT-dependent increase of the cGMP content was notable. Platelet $Ins(1,4,5)P_3$ content was rapidly increased up to a plateau within 10 sec after thrombin-stimulation, AMT, SRT, and CPZ increased the basal $Ins(1,4,5)P_3$ content, and the thrombin-dependent increase was enhanced by pretreatment with CPZ and AMT, but was blunted by SRT. Platelet $[Ca^{2+}]_i$, was rapidly increased up to a peak level within 20 sec after thrombin-stimulation. The increase of $[Ca^{2+}]_i$ was sisnificantly inhibited by AMT, SRT, and CPZ. Thrombin- or PMA-induced phosphorylations of platelet $41{\sim}43\;kDa$ and 20 kDa proteins were significantly inhibited by AMT, SRT, and CPZ. These results suggest that the antiplatelet activities of AMT and CPZ may be considerably attributed to the inhibition of protein kinase C activity, and the activity of SRT may be associated with the inhibitory effect on the thrombin-induced increase of $Ins(1,4,5)P_3$ and the increasing effect on the cGMP content of ptatelets. Therefore, it seems to be evident that AMT and SRT may produce their antidepressant activity, at least, partly through the inhibition of protein kinase C activity or the increase of resting $Ins(1,4,5)P_3$, content and in case of SRT, to a lesser extent, via the increase of cGMP in the brain.

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Impacts of Green Manure Crop and Charcoal Applications on Ginger Growth and Soil Properties (녹비작물 및 Charcoal 처리가 생강 생육 및 토양 특성에 미치는 영향)

  • Yang, Hong-Seok;Kim, Dong-Jin;Ahn, Byung-Koo;Lee, Jin-Ho
    • Korean Journal of Organic Agriculture
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    • v.22 no.3
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    • pp.503-519
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    • 2014
  • This study was conducted to investigate ginger growth and its nutrient uptake depending on changes of soil properties as affected by applications of green manure crop and/or charcoal in continuous cropping system. The green manure crops applied were barley and hairy vetch, and charcoal was additionally treated in selected plots as a soil conditioner. Experimental plots were prepared as Plot 1 (control), Plot 2 (barley of 8kg $10a^{-1}$), Plot 3 (hairy vetch of 12kg $10a^{-1}$), Plot 4 (charcoal of 1,000kg $10a^{-1}$ and barley 8kg $10a^{-1}$), and Plot 5 (charcoal of 1,000kg $10a^{-1}$ and hairy vetch of 12kg $10a^{-1}$) with two different soil conditions (high clay content, HCC and low clay content, LCC). When comparing selected chemical properties of soils before and after cultivating ginger plant, soil pH decreased from 6.9~8.1 to 6.8~7.6, and electrical conductivity (EC) also declined from $0.45{\sim}1.25dSm^{-1}$ to $0.30{\sim}0.61dSm^{-1}$. However, the content of soil organic matter (SOM) and total nitrogen (T-N) increased. Thus, the soil chemical properties were improved with the applications of green manures and charcoal. Also, macro- and micro-nutrient contents of ginger plants in the different plots were various between normal and diseased plants grown in soils with HCC and LCC. In particular, the concentration of manganese (Mn) was 3~4 folds higher in the diseased plant than in the normal plants. Ginger growth status and yield was relatively improved with the applications of green manures and charcoal as comparing with control plot. Especially in the Plot 4 with LCC, the ginger plant was not infected by root-rot disease.

Inhibitory Role of Polyamines in Dexamethasone-induced Apoptosis of Mouse Thymocytes (Dexamethasone에 의한 생쥐 흉선의 Apoptosis에서 Polyamine의 역할)

  • Choi, Sang-Hyun;Kim, Yong-Hoon;Hong, Gi-Hyun;Shin, Kyung-Ho;Chun, Yeon-Sook;Chun, Boe-Gwun
    • The Korean Journal of Pharmacology
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    • v.32 no.1
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    • pp.113-123
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    • 1996
  • It has been well known that polyamines ensure the stability of chromatin structure and the fidelity of DNA transcription. This study was carried out to evaluate the effect of polyamines on the apoptosis of mouse thymocytes induced by dexamethasone and polyamine synthesis inhibitors. 1) In the histological death findings of thymocytes double-stained with acridine orange and ethidium bromide, the apoptotic and the necrotic fractions (AF; NF) in the control group were $9.4{\pm}4.2%$ and $4.5{\pm}5.3%$, respectively. Dexamethasone $(3\;{\times}\;10^{-8}\;M:\;DX)$ in creased AF upto $52.0{\pm}8.1%$ and did not change NF, but A23187 $(5\;{\times}\;10^{-7}\;M:\;A2)$ increased AF and NF upto $45.0{\pm}8.9%$ and $20.5{\pm}10.6%$, respectively. 2) The thymocyte viability was significantly reduced by DX, DHEA $(1\;{\times}\;10^{-4}\;M)$, A2, DFMO $(1\;{\times}\;10^{-4}\;M)$, and $MGBG\;(1\;{\times}\;10^{-4}\;M)$, respectively. It was, however, little affected by $aminoguanidine\;(1\;{\times}\;10^{-4}\;M:\;AG)$, $putrescine\;(1\;{\times}\;10^{-5}\;M:\;PT)$, $spermidine\;(1\;{\times}\;10^{-5}\;M:\;SD)$, and $spermine\;(1\;{\times}\;10^{-5}\;M:\;SM)$. 3) The genomic DNA of mouse thymocyte was markedly fragmented by DX and A2, respectively, and to a lesser extent, by DHEA, but was little affected by MGBG, DFMO, AG, and each of polyamines. 4) The DX induced reduction of thymocyte viability was moderately attenuated by DHEA, but little affected by DFMO, MGBC, and AG. However, SM significantly attenuated the viability reduction induced by A2 as well as DX. 5) The thymocyte viability reduction by MGBG and DFMO was significantly attenuated by only SM among three polyamines applied in this study. 6) The thymocyte viability redution by combined treatments of DX with DFMO and MGBG, respectively, was significantly attenuated by SM, and moderately by PT. But the viability reduction by combined treatment of DX with AG or DHEA was not affected by polyamines. These results suggest that polyamines, particularly spermine, might play the inhibitory role in thymocyte apoptosis and the inhibitory effect can be ascribed in part to the increase of polyamine uptake by thymocytes pretreated with DFMO and MGBG.

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