• YAKHAK HOEJI
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• v.38 no.5
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• pp.488-495
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• 1994

To evaluate the feasibility of transmucosal delivery of leucine enkephalin (Leu-Enk) and its synthetic analog, $[D-Ala^2]$-leucine enkephalinamide (YAGFL), their physicochemical stabilities in aqueous buffered solutions were first investigated using a stability indicating high performance liquid chromatography. The degradation of Leu-Enk and YAGFL followed the pseudo-first-order kinetics. From the pH-rate profiles, it was found that the maximal stability of the two pentapeptides was at the pH of about 5.0. The shelf lives $(t_{90%})$ for the degradation of Leu-Enk and YAGFL at pH 5.0 and $40^{\circ}C$ were found to be 48.13 and 50.9 days, respectively. From the temperature dependence of the degradation, activation energies for Leu-Enk and YAGFL were calculated to be 13.61 and 13.47 kcal/mole, respectively. A higher ionic strength and a higher initial peptide concentration in buffered solution slowed the degradation of the two pentapeptides. The addition of 2-hydroxypropyl-${\beta}$-cyclodextrin into the peptide solution did not affect the stability significantly.

• Journal of Korean Neurosurgical Society
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• v.30 no.4
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• pp.417-424
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• 2001

Objective : Adrenal medullary chromaffin cells are known to release analgesic substances such as opioides and catecholamines. Transplantation of them is a novel method that challenges current approaches in treating chronic pain. The transplantation of xenogeneic chromaffin cells into the central nervous system(CNS) supply antinociception in animals. In this study, we investigated the analgesic effects of rat adrenal medullary chromaffin cells transplanted into the CNS of the mouse. To study the antinociceptive efficacy of transplanted chromaffin cells, the survival of rat adrenal medullary chromaffin cells transplanted into the CNS of mouse was determined. Methods : The adrenal medullary chromaffin cells isolated from rat were transplanted into the striatum of mouse. These cells were confirmed of the release of Met-enkephalin and Leu-enkephalin by HPLC, and immunoblots for tyrosine hydroxylase(TH). Two weeks after transplantation, we performed immunohistochemistry for TH to determine the survival of implanted cells and assessed pain sensitivity at the same time. Results : The isolated rat adrenal medullary chromaffin cells were positive for anti-TH antibody and released Met-enkephalin and Leu-enkephalin more than rat endothelial cells. Transplanted rat chromaffin cells were stained with anti-TH antibody in striatum of mouse after 2 weeks. Pain sensitivity was reduced on the chromaffin cell-transplanted mouse compared to endothelial cell-transplanted mouse by the hot plate test. Conclusion : These results suggest that the rat chromaffin cells were suitably transplanted into the CNS of mouse. This approach could be used as a therapy for reducing of chronic pain induced by cancer or neuronal injury.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.8
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• pp.5336-5342
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• 2015

Although demand for scar treatment has been rising as our quality of life is improved, most scar treatment products rely on importation. Enkephalin is one of the neuropeptides secreted from neuronal ends. As both skin and neuron are derived from the exoderm during the development process, skin cells express opioid receptors as neuronal cells do. Opioid receptors are categorized into three types, mu(m)-, delta(d)-, and kappa(k)- opioid receptors, all of which are directly involved in the wound healing process. In this study, enkephalin derivatives are synthesized by Alanin Scan and their efficacy was evaluated and compared. In vitro wound healing effects, stimulatory effects of collagen synthesis, and skin hydration effects were also evaluated and confirmed. Among Enkephalin derivatives, AS13 showed highest wound healing effect.

• Bulletin of the Korean Chemical Society
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• v.18 no.7
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• pp.778-781
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• 1997

• Bulletin of the Korean Chemical Society
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• v.6 no.6
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• pp.380-381
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• 1985

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.31-36
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• 1993

To evaluate the feasibility of transmucosal delivery of methionine enkephalin analog, [$D-Ala^2$]-me-thionine enkephalinamide (YAGFM), the influence of pH, temperature, ionic strength and initial peptide concentration on the physicochemical stability of YAGFM in aqueous buffered solutions were investigated using a stability-indicating HPLC method. The degradation of YAGFM followed the pseudo-first-order kinetics. From the pH-rate profile, the maximum stability of YAGFM was shown to be at the pH of about 5.0. The halflife for the degradation of YAGFM was found to be 181.3 days at pH 5.0 and $37^{\circ}C.$ Arrhenius plots of the data obtained at 25~$45^{\circ}C$ were reasonably linear with a correlation coefficient greater than 0.99, and the activation energy was calculated to be 8.9 kcal/mole. A higher ionic strength and/or a higher peptide concentration in buffered solutions retarded the degradation of YAGFM.

• Toxicological Research
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• v.9 no.2
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• pp.187-194
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• 1993

[Met5]-Enkephalin (ME) secretion and the expression of proenkephalin A (proENK) mRNA were studied following long-term exposure of bovine adrenal medullary chromaffin (BAMC) cells to pertussis toxin. Prolonged (24 hr) stimulation of BAMC cells with pertussis toxin increased the secretion of ME as well as proENK gene expression. BAMC cells were also incubated with pertussis toxin in the presence or absence of other secretagogues such as nicotine, angiotensin II and phorbol myristate acetate.

• Bulletin of the Korean Chemical Society
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• v.14 no.4
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• pp.419-420
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• 1993

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.153-164
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• 1988

The potential role of endogenous opioid peptides (EOPS) in cardiovascular regulation has only recently been entertained. EOPS have been localized in brain, spinal cord, autonomic ganglia, particularly the adrenal gland, and many other peripheral tissues. There are at least five major types of opioid receptors; namely ${\mu},\;{\delta},\;k,\;{\sigma},\;and\;{\varepsilon}$ and Experimental evidence indicates that cardiovascular actions of the peptide are mediated primarily by ${\mu},\;{\delta}$ and k receptors, and that these receptor types may be allosterically coupled. In anesthetized rabbits met-enkephalin decreased blood pressure and heart rate, which closely paralleled a reduction in sympathetic discharge. Naloxone, but not naloxone methobromide, antagonized these effects, which suggests a central site of action of met-enkephalin. A number of autonomic agents, particularly adrenergic ${\alpha}$-and, ${\beta}-agonists$ and antagonists modify the cardiovascular actions of met-enkephalin. Experiments in reserpine-treated and adrenalectomized rats provide no evidence of sympathetic nervous system involvement in the pressor responses to intravenous injection of opioid peptides, but rather suggest a direct peripheral action. Finally, activation of a beta-endorphinergic pathway projecting from the arcuate nucleus to the nucleus tractos solitarii in rats can cause naloxone reversible hypotension and bradycardia. There is evidence to implicate this pathway in antihypertensive drug action and in the modulation of baroreflex activity.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.109-114
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• 1997

The effect of total saponin fraction of Ginseng injected intrathecally (i.1.) or in- tracerebroventricularly (i.c.v.) on the antinociception induced by D-$Pen^{2,5}$- enkephalin (DPDPE) ad ministered i.c.v. was studied in ICR mice in the present study. The antinociception was assessed by the tail-flick test. Total saponin fraction at doses 0.1 to 1.0 $\mu\textrm{g}$, which administered i.t. Alone did not affect the latencies of tail-flick threshold, attenuated dose-dependently the inhibition of the tail-flick response induced by i.c.v. administered DPDPE (10 $\mu\textrm{g}$). However, total saponin fraction at doses 1 to 20 $\mu\textrm{g}$, which administered i.c.v. Alone did not affect the latencies of the tail-flick response, did not affect i.c.v. administered DPDPE (10 $\mu\textrm{g}$)-induced antinociception. The duration of antagonistic action of total saponin fraction against DPDPE-induced antlnociception was lasted at least for 6 hrs. Various doses of ginsenosides Rd, but not $\Rb_2$, Rc, Rg1, and $\Rb_1$ and Re, injected i.t. Dose-dependently attenuated antinociception induced by DPDPE administered i.c.v. Our results indicate that total saponin fraction injected spinally appears to have antagonistic action against the antinociception induced by supraspinally applied DPDPE. Ginsenoside Rd appears to be responsible for blocking j.c.v. administered DPDPE-induced antinociception. On the other hand, total ginseng fraction, at supraspinal sites, may not have an antagonistic action against the antinociception induced by DPDPE.