• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.5
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• pp.402-407
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• 2006

Vascular endothelial cells release proteinases that degrade the extracellular matrix (ECM), thus enabling cell migration during angiogenesis and vasculogenesis. Sildenafil citrate stimulates the nitric oxide-cyclic guanosine monophosphate pathway through inhibition of phosphodiesterase type V (PDE5). In this report, we examined the mechanisms underlying sildenafil citrate-induced cell migration using cultured mouse aortic endothelial cells (MAECs). Sildenafil citrate induced migration and proteinase secretion by murine endothelial cells. Sildenafil citrate induced the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9, which is inhibited by $NF-{\kappa}B$ inhibitors. Sildenafil citrate also induced the secretion of plasmin, which is inhibited by PI 3'-kinase inhibitors. It is suggested that sildenafil citrate-induced migrating activity in endothelial cells may be accomplished by increased secretion of proteinases.

• Bulletin of the Korean Chemical Society
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• v.17 no.1
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• pp.24-28
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• 1996

A procedure is described for the synthesis of the title compound via phosphotriester intermediates. The preparation of $R_p$ and $S_p$ diastereomeric dinucleotide of d[Cp(S)T] was performed by the condensation of the protected deoxycytidine, the protected thymidine, 2,5-dichlorophenylphosphorodichloridothioate and 1-hydroxybenzotriazole in THF. Their designation of configuration at phosphorus as $R_p$ and $S_p$ follows from anaylsis of ${31}^P$ NMR spectroscopy and reverse-phase HPLC and the stereospecificity in the hydrolysis catalyzed by Nuclease S1 and snake venom phosphodiesterase. Diastereomerically pure $R_p$ and $S_p$ d[Cp(S)T] were utilized to synthesize oligonucleotides containing the XhoI recognition sequence with a phosphorothioate group at the cleavage site.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.11
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• pp.1571-1579
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• 2016

We investigated the effect of peanut sprout extract (PSE) on andropause symptoms. PSE was evaluated for impotency and benign prostatic hyperplasia via phosphodiesterase (PDE) or 5-alpha reductase II inhibition assay. Inhibition of PDE and 5-alpha reductase II activities in PSE was significantly higher than that of the non-treated control. To investigate the effects of testosterone levels by PSE, we performed cell media test using TM3 cells. Production of testosterone in TM3 cells was elevated by PSE. These results indicate that PSE was able to alleviate andropause symptoms.

• Archives of Pharmacal Research
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• v.28 no.6
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• pp.675-679
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• 2005

Eight furoquinoline alkaloids were purified from two plants belonging to the Rutaceae family. Kokusaginine. skimmianine, evolitrine, and confusameline were purified from Melicope confusa, and haplopine, robustine, dictamine, and $\gamma$-fagarine from Dictamnus albus. In this study, the eight furoquinoline alkaloids were examined for inhibitory potency against human phos-phodiesterase 5 (hPDE5A) in vitro. DNA encoding the catalytic domain of human PDE5A was amplified from the mRNA of T24 cells by RT-PCR and was fused to GST in an expression vector. GST-tagged PDE5A was then purified by glutathione affinity chromatography and used in inhibition assays. Of the eight alkaloids, $\gamma$-fagarine was the most potent inhibitor of PDE5A, and its single methoxy group at the C-8 position was shown to be critical for inhibitory activity. These results clearly illustrate the relationship between PDE5A inhibition and the methoxy group position in furoquinoline alkaloids.

• Korean Journal of Clinical Pharmacy
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• v.3 no.2
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• pp.147-155
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• 1993

The cardiac effects of PAF antagonist Ginkgolide B(BN 52051) have been investigated on the isolated perfused guinea pig hearts maintained at the constant hydrostatic perfusion pressure of 80 cm water. PDE(Phosphodiesterase) inhibitor KR-30289 was used as a positive control to see the positive inotropic effects on the perfused hearts. In this expriments, Ginkgolide $B(10^{-5}-SM)$ showed negative inotropic effects by decreasing of LVP, LVDP, LV dp/dt, HR and RPP(Rate Pressure Product). Ginkgolide B also decreased the number of extrasystole by $51.9\%(from\;23.75\pm9.22/min\;to\;11.43\pm435/min)$ induced by global ischemia and reperfusion. The rate, [-dp/dt]/[+dp/dt] increased in preischemia but decreased in postischemia. 1n the separated study the injection of 1ml of Ginkgolide B$(10^{-4M})$ on the isolated heart, increased coronary flow(CF) by $11.8\%(from\;7.5\pm7.65ml/min\;to\;8.5\pm0.29ml/min)$ and decreased the number of extrasystole by $47.6\%(from\;21\pm5.92/min\;to\;11\pm5.27/min)$. In conclusion, Ginkgolide B showed antiarrhythmic and protective effects by decreasing the number of extrasystole and by increasing the coronary flow, respectively.

• YAKHAK HOEJI
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• v.41 no.5
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• pp.652-657
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• 1997

We studied the effects of sulfasalazine(SSZ) on anaphylaxis. SSZ was found to exhibit a inhibitory activity on the compound 48/80-induced anaphylaxis. SSZ also inhibited local a naphylaxis activated by anti-dinitrophenyl(DNP) IgE. Moreover, SSZ dose-dependently inhibited histamine ralease in rat peritoneal mast cells activated by compound 48/80 or anti DNP IgE. We investigated the effects of SSZ on cAMP of rat peritoneal mast cell. The level of cAMP in rat peritoneal mast cells, when SSZ was added, transiently and significantly increased approximately 16-fold compared with that of basal cells. These results suggest that the antianaphylactic action of SSZ may be associated with an increase in the intracellular cAMP content of the mast cells as the result of an inhibition of the cAMP phosphodiesterase.

• YAKHAK HOEJI
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• v.54 no.5
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• pp.410-415
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• 2010

We explored the role of phosphodiesterase 4 (PDE4) on parathyroid (PTH)-induced signaling in osteoblasts. PTH was shown to increase the activity of PDE, mainly PDE4, in osteoblasts, which is partly attributable to elevated PDE4B and PDE4D mRNA expression. The use of PDE4 inhibitor strengthened the PTH-induced extracellular signal-regulated kinase (ERK) and p38 MAP kinase (MAPK) activation. Furthermore, the PDE4 inhibitor stimulated PTH-induced receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) expression in osteoblasts, which in turn increased osteoclast formation. Taken together, these data suggest the negative role of PDE4 on PTH-induced signaling in osteoblasts.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.245.1-245.1
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• 2003

DA-8159 is a new PDEV (Phosphodiesterase V) inhibitor, synthesized by Dong-A Pharm., as an oral agent to treat male erectile dysfunction. To make a selection of the dosage of oral administration in carcinogenic studies, we studied preliminarily the pharmacokinetics of DA-8159 after single (at the 1$\^$st/ day) and 1-week (at the 7$\^$th/ day) oral administrations of the drug at doses of 15, 50 and 150 mg/kg/day, to male ICR mice. In 15mg/kg single and 1-week repeated oral administration groups, the concentrations of DA-8159 and DA-8164(the main metabolite of DA-8159) were below the limit of quantitation(LOQ:50ng/ml). (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.155-155
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• 1993

항우울약인 rolipran(RP)등 phosphodiesterase-억제 약(PDE-1)들이 thrombin(TB: 0.25 U/ml)에 의한 혈소판 응집에 미치는 작용을 가토-혈소판에서 일차 검토하였다. 신 PDE-1인 KR-30075(KR)의 $IC_{50}$/은 sodim nitroprusside의 것보다 낮았고 PDE-1들은 혈소판내 cAMP와 cGMP를 증가시켰으며 특히 KR은 타 PDE-1와 달리 I $P_3$를 감소시켰다. 아울러 rolipram은 cGMP와 I $P_3$를 증가시켰으나, amitriptyline(AT), sertraline(57), chlorpromazine(CP) 및 spermine은 I $P_3$를 증가시켰다. 그러나 이들과 PDE-1들은 강도의 차이는 있으나 모두 TB에 의한 혈소판응집을 모두 억제하였다. 따라서, PDE-1 중 IBMX(2$\times$$10^{-5}$M), KR(5$\times$10$_－7/M), 및 rolipram(10$_{-3}$M) 그 외에 항우울약인 AT(1.5 $\times$10$_－4/M) 와 ST(10$_－4/M) 및 항정신병약인 CP(10$_－4/M)둥이 혈소판내 I $P_3$, [C $a^{＋＋}$], Tx $B_2$, 및 PG $I_2$ 함량과 단백-인산화의 TB에 의한 변동에 미치는 영향을 검토하였다. 그 결과 TB에 의한 혈소판내 I $P_3$, [C $a^{＋＋}$], Tx $B_2$, 및 PG $I_2$ 함량의 증가가 PDE-1들과 항우울약들에 의하여 억제되었다 단, 항우울성약들과 CP는 정상 혈소판 I $P_3$를 증가시켰다. 아울러 혈소판-단백인산학에서 TB는 41-43 kD와 20 kD의 인산화를 현저히 증가시키며 19 kD의 인산화는 감소시켰고, PKC의 기질인 41-43 kD와 20 kD의 단백인산화가 PDE-1들과 항우울약들 뿐 아니라 CP에 의하여 현저히 억제되었다. 단, 20 kD 인산화에 대한 AT의 억제작용은 미약하였고, cAMP와 PDE-1들은 22kD 인산화를 증가시켰다. AT, ST, 및 CP는 A23187에 의한 41-43 kD 인산화는 현저히 억제하나 20 kD 인산화에는 영향을 미치지 않았고, PMA(3.2$\times$$10^{－7}$ M)에 의한 단백인산화에 대하여는 더 미약한 억제-효과를 나타내었다. 이상의 결과는 PDE-1과 항우울약들의 항혈소판작용은 PKC-기질인 41-43 kD와 20 kD의 인산화를 억제함에 기인되는 것으로 사료된다.다. 것으로 사료된다.다.

• Korean Journal of Animal Reproduction
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• v.25 no.4
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• pp.349-357
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• 2001

This study was conducted to examine the effect of caffeine and three dietary levels of fat, i.e., 0%, 5% and 20% on mammary gland development. Mice were assigned to three groups (dietary levels 0%, 5%, 20% fat), and treated caffeine of half within the each group. Caffeine-treated mice with 0% or 20% fat levels significantly increased 4$^{th}$ mammary gland development in comparison with that of no caffeine -treated mice (P＜0.05). Caffeine-treated mice significantly increased DNA contents of 4$^{th}$ mammary gland in comparison with that of no caffeine-treated mice (P＜0.05), and DNA contents of mammary gland increased as fat levels increased within caffeine-treated or no caffeine-treated group. nteraction effect was shown between caffeine and 20% fat diet, ［(20% fat+caffeine) - (20% fat + no caffeine) vs (0% fat + caffeine) - (0% fat + no caffeine)］(P＜0.01). Conclusively, caffeine significantly increased mouse mammary gland development possibly by inhibiting phosphodiesterase activity, and dietary fat supplements increased mammary gland development as the fat content of the diet increased from 0 to 20%. The stimulatory effect of caffeine in mammary development interacted with high level of fat diet.