• Title, Summary, Keyword: D-Leu^5]-enkephalin$ (DADLE)

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Effects of a ${\delta}-opioid$ Agonist on the Brainstem Vestibular Nuclear Neuronal Activity of Rats

  • Kim, Tae-Sun;Huang, Mei;Jang, Myung-Joo;Jeong, Han-Seong;Park, Jong-Seong
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.3
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    • pp.137-141
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    • 2005
  • This study was undertaken to investigate the effects of [$D-Ala^2$, D-Leu^5$]-enkephalin (DADLE) on the spontaneous activity of medial vestibular nuclear neurons of the rat. Sprague-Dawley rats, aged 14 to 16 days, were anesthetized with ether and decapitated. After enzymatic digestion, the brain stem portion of medial vestibular nuclear neuron was obtained by micropunching. The dissociated neurons were transferred to a recording chamber mounted on an inverted microscope, and spontaneous action potentials were recorded by standard patch-clamp techniques. The spontaneous action potentials were increased by DADLE in 12 cells and decreased in 3 cells. The spike frequency and resting membrane potential of these cells were increased by DADLE. The depth of afterhyperpolarization was not affected by DADLE. The potassium currents were decreased in 20 cells and increased in 5 cells. These results suggest that DADLE increases the neuronal activity of the medial vestibular nuclear neurons by altering resting membrane potential.

Cell Cycle Arrest by Treatment of D-Ala2-Leu5-enkephalin in Human Leukemia Cancer U937 Cell. (인체혈구암세포 U937의 D-Ala2-Leu5-enkephalin처리에 의한 세포 주기 억제 효과)

  • Lee, Jun-Hyuk;Choi, Woo-Young;Choi, Yung-Hyun;Choi, Byung-Tae
    • Journal of Life Science
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    • v.19 no.5
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    • pp.620-624
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    • 2009
  • D-Ala2-Leu5-enkephalin (DADLE), a hibernation inducer, can induce hibernation-like state in vivo and in vitro. We treated U937 human leukemia cancer cells with DADLE and investigated its possible effect on transcription and proliferation. Treatment of U937 cells with DADLE resulted in growth inhibition and induction of apoptotic cell death on high-dose as measured by MTT assay and DNA flow cytometer analysis. Bcl-XL, c-IAP-2 and survivin genes especially showed decreases in mRNA levels. DADLE treatment also inhibited the levels of cyclooxygenase (COX)-2 mRNA without alteration of COX-1 expression. DNA flow cytometer analysis revealed that DADLE caused arrest of the cell cycle on low-dose, which was associated with a down-regulation of cyclin E at the transcriptional level. DADLE treatment induced a marked down-regulation of cyclin-dependent kinase (Cdk)-2, -4 and -6. In addition, treatment with DADLE decreased telomere associated genes such as, c-myc and TERT, and increased TEP-1 in U937 cells. These results suggest that DADLE can be an inhibition agent in the cell cycle of the human leukemia cancer U937 cell.

Buccal Delivery of [D-Ala2, D-Leu5]Enkephalin Incorporated in Mucoadhesive Poly(acrylic acid) Hydrogels

  • Lee, Jae-Hwi;Lee, Yoon-Jin;Kang, Kyoung-Hoon;Nam, Dae-Young;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.35 no.5
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    • pp.369-373
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    • 2005
  • The objectives of the current work is to understand the factors impacting the formulation and performance of a Carbopol mucoadhesive buccal delvery system for a model peptide drug, $[D-Ala{^2},\;D-Leu{^5}]$enkephalin (DADLE, Mw=569.7) with comparable chemical and enzymatic stability. Specifically, in vitro buccal DADLE delivery from the cross-linked poly(acrylic acid) (PAA) hydrogel system was characterized. In addition, the influences of several penetration enhancers on the ex vivo buccal absorption of DADLE were also studied. In this study, the PAA hydrogels generally swell to 100% of their original weight in the phosphate pH 7.4 buffer. The water penetration into the PAA hydrogel occurred based on a zero-order kinetics for the first 60 min and steadily decreased afterwards. From the release study, it can be seen that the initial DADLE release was so rapid and the rate of release of DADLE decreased as the time elapsed. The porcine buccal tissue was found to be permeable to DADLE with a flux value of $0.07%/cm{^2}/hr({\pm}0.01\;SD)$. From the ex vivo diffusion study, it was found that sodium taurodihydrofusidate showed a greater degree of enhancement compared to the phospholipids with an Enhancement Ratio (ER) of 8.7 compared to 2.7 and 1.9 for didecanoylphosphatidylcholine and lysophosphatidylcholine, respectively. The work encompassed within this paper has demonstrated the feasibility of using the PAA hydrogel delivery system with its good mucoadhesive properties for the buccal delivery of peptides.