• Journal of Pharmaceutical Investigation
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• v.23 no.1
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• pp.1-9
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• 1993

The endothelial cell of brain capillary called the blood-brain barrier (BBB) has carrier-mediated transport systems for nutrients and drugs. The mechanism of the BBB transport of basic and acidic drugs has been reviewed and examined for endogenous transport systems in BBB in WKY and SHRSP. Acidic drugs such as salicylic acid and basic drugs such as eperisone are taken up in a carrier mediated manner through the BBB via the monocarboxylic acid and amine transport systems. The specific dysfunction for the choline transport at the BBB in SHRSP would affect the function of the brain endothelial cell and brain parenchymal cell. The utilization of the endogenous transport systems of monocarboxylic acid and amine could be promising strategy for the effective drug delivery to the brain.

• The Korean Journal of Pharmacology
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• v.6 no.1
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• pp.15-22
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• 1970

The present study is concerned with the demonstration of the relationship between the behavior and the brain concentration of noradrenaline resulted from pretreatment of amphetamine in isolated or aggregated rats. The experimental subjects were rats weighing from 120g to 200g housed 1, 2, and 6 in a cage. Analeptic activity of amphetamine was measured by determining the sleeping time induced by pentobarbital sod. The noradrenaline content in brain was determined with Aminco-Bowmann's spectro-photofluorometer by Lee's modification of Shore and Olin method. Results: 1) The analeptic activity of amphetamine on the sleeping time induced by pentobarbital sod. was more increased in the grouped rats than in isolated animal. 2) In being isolated and grouped rats, the sleeping time induced pentobarital sod, was markedly prolonged by pretreatment of amphetamine. 3) Means of housing rats, e.g., isolation or aggregation did not seem to affect the brain noradrenaline depleting action. 4) Repeated daily parenteral administration of amphetamine sulfate for a period 1 to 3 weeks resulted in decrement of brain noradrenaline concentration in being isolated and grouped rats. 5) The prolongation of sleeping time of the isolated or aggregated rats, when pretreated with amphetamine, compared with that of stock rats, seems to be attributable rather to the means of housing than the variation of the noradrenaline caused by amphetamine.

• Applied Biological Chemistry
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• v.38 no.4
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• pp.320-324
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• 1995

Solubilization of microsomal ${\Delta}^{5}-3{\beta}$-hydroxy steroid acyl transfearse(${\Delta}^{5}-3{\beta}$-OH-SAT) of rat brain and its reconstitution into liposomes were investigated. Among the detergents utilized for the solubilization, deoxycholic acid was superior to Tween 80 or Triton X-100 for the reconstituted activity of ${\Delta}^{5}-3{\beta}$-OH-SAT. The enzyme activity was shown to be affected by the nature of phospholipids used for the preparation of the liposome. Phosphatidylcholines from egg yolk and soybean showed the highest activity of ${\Delta}^{5}-3{\beta}$-OH-SAT and phosphatidylethanolamine came next. However phosphatidylserine and phosphatidic acid showed a lower activity than those obtained before the reconstitution. This study suggests that the presence of quaternary ammonium salt or amine group in the phospholipids stimulates the activity of ${\Delta}^{5}-3{\beta}$-OH-SAT. However the presence of a carboxylic group or the absence of the amine group may have an inhibitory effect on the ${\Delta}^{5}-3{\beta}$-OH SAT.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.107-107
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• 2003

The purpose of this study is to examine that the efflux transport system for choline from brain to blood is present at the blood-brain barrier (BBB) using brain efflux index (BEI) method. ［$^3$H］Choline was microinjected into parietal cortex area 2 (Par2) region of rat brain, and was eliminated from the brain with an apparent elimination half life of 45 min. The BBB efflux clearance of ［$^3$H］choline was 0.12 $m\ell$/min/g brain, which was calculated from the efflux rate constant (1.5${\times}$10$\^$-2/ min$\^$-1/) and the distribution volume in the brain slice (8.1 $m\ell$/g brain). This process was saturable and significantly inhibited by various organic cationic compounds including hemicholinium-3, tetraethylammonium chloride (TEA) and verapamil, by antioxidant, ${\alpha}$-phenyl-n-tert-butyl nitrone (PBN), and by Alzheimer's disease therapeutics, such as acetyl $\ell$-carnitine and tacrine. In conclusion, this finding is the first direct in vivo evidence that choline is transported from brain to the blood across the BBB via a carrier-mediated efflux transport process.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.443-450
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• 2005

In the present study, we have characterized the choline transport system and examined the influence of various amine drugs on the choline transporter using a conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) in vitro. The cell-to-medium (C/M) ratio of $[^3{H}]choline$ in TR-BBB cells increased time-dependently. The initial uptake rate of $[^3{H}]choline$ was concentration-dependent with a Michaelis-Menten value, $K_{m}$, of $26.2\pm2.7{\mu}M$. The $[^3{H}]choline$ uptake into TR-BBB was $Na^{+}-independent$, but was membrane potential-dependent. The $[^3{H}]choline$ uptake was susceptible to inhibition by hemicholinium-3, and tetraethy-lammonium (TEA), which are organic cation transporter substrates. Also, the uptake of $[^3{H}]choline$ was competitively inhibited with $K_{i}$ values of $274 {\mu}M, 251 {\mu}M and 180 {\mu}M$ in the presence of donepezil hydrochloride, tacrine and $\alpha-phenyl-n-tert-butyl nitrone$ (PBN), respectively. These characteristics of choline transport are consistent with those of the organic cation transporter (OCT). OCT2 mRNA was expressed in TR-BBB cells, while the expression of OCT3 or choline transporter (CHT) was not detected. Accordingly, these results suggest that OCT2 is a candidate for choline transport at the BBB and may influence the BBB permeability of amine drugs.

• Bulletin of the Korean Chemical Society
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• v.35 no.5
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• pp.1269-1274
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• 2014

Monoamine oxidases catalyze the oxidative deamination of dietary amines and amine neurotransmitters, and assist in maintaining the homeostasis of the amine neurotransmitters in the brain. Dysfunctions of these enzymes can cause neurological and behavioral disorders including Parkinson's and Alzheimer's diseases. To understand their physiological roles, efficient assay methods for monoamine oxidases are essential. Reviewed in this Perspective are the recent progress in the development of fluorescent probes for monoamine oxidases and their applications to enzyme assays in cells and tissues. It is evident that still there is strong need for a fluorescent probe with desirable substrate selectivity and photophysical properties to challenge the much unsolved issues associated with the enzymes and the diseases.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.153-164
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• 1995

Sympathomimetic amines, especially ephedrine, are a major ingredient in proprietary medications for symptomatic treatment of upper respiratory infections. Their frequent uses can lead to occasional instances of abuse and habituation. The clinical symptoms of ephedrine abuse are similar to that of amphetamine psychosis and resemble closely that of schizophrenia. Because both amphetamine psychosis and schizophrenia are thought to be mediated primarily through the action on catecholamines, ephedrine-induced changes of the biogenic amines can be suspected. However, there were few studies about the central effects of ephedrine because of the milder central action than peripheral. Therefore, the present investigation was undertaken to elucidate the relations between the effects of single or repeated administration of ephedrine on the regional levels of biogenic amines in rat brain and ephedrine-induced CNS stimulation. The male Sprague-Dawley rats weighing $100{\sim}200\;g$ were used. After single or repeated administrations of ephedrine, blocks of tissue were obtained from frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substantia nigra and cerebellum. The concentration of biogenic amines(norepinephrine, epinephrine, dopamine, 5-hydroxytryptamine(5-HT)) and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA)) were measured by means of high performance liquid chromatography-electrochemical detector(HPLC-ECD). The results obtained were as follows: 1) In the normal rat, the concentration of norepinephrine was the highest in hypothalamus. Dopamine, DOPAC and HVA were highest in corpus striatum, and 5-HT and 5-HIAA were highest in substantia nigra. Epinephrine was not detectable in any part of the brain tissue. 2) In a single administration of ephedrine, the concentration of DOPAC was decreased in corpus striatum. However, the other biogenic amines and their metabolites were not changed. 3) In repeated administration of ephedrine, the concentration of norepinephrine was decreased in all brain region checked. Dopamine was decreased in corpus striatum and substantia nigra and, increased in hypothalamus, and HVA was decreased in corpus striatum. 5-HT was decreased in all brain region except cerebellum and, 5-HIAA was decreased only in frontal cortex. The ratio of 5-HIAA/5-HT was increased in corpus striatum, thalamus, hypothalamus and substantia nigra. These data indicated that, although a single administration of ephedrine did not change the central neurotransmitters, repeated administration of ephedrine caused the decreases of norepinephrine and 5-HT in the most regions of brain, which may be responsible for the emergence of abnormal behavioral effect after ephedrine abuse.

• YAKHAK HOEJI
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• v.36 no.5
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• pp.427-432
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• 1992

We attempted to clarify the effect of bilateral olfactory bulbectomy on catalepsy induced by haloperidol in rats. The incidence of catalepsy induced by haloperidol remarkably increased after lesion of olfactory bulb, which was significantly inhibited by L-5-hydroxytryptophan, L-DOPA, and ginseng's total saponin but reserpine and ${\alpha}-methyl-p-tyrosine$ were ineffective. The dopamine content of brain was significantly decreased by olfactory bulbectomy, but this result was reversed by ginseng's total saponin.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.139-142
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• 1998

The effects of MeOH extracts from 28 herbal medicines on monoamine oxidase (MAO) activity were investigated. MAO was purified from mouse brain and its activity was determined by fluoro-photometry using kynuramine as a substrate. Three MeOH extracts, Coptis japonica, Cinnamomum cassia and Poncirus trifoliate from the herbal medicines showed a strong inhibitory effect with less than $100\;{\mu}g/ml$ in their inhibitory amounts of $50\%$ ($IC_{50}$ values) on MAO activity. Four MeOH extracts including Evodia officinalis exhibited a mild inhibition of MAO activity with $100-200\;{\mu}g/ml$ in their $IC_{50}$ values.

• Bulletin of the Korean Chemical Society
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• v.30 no.6
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• pp.1357-1359
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• 2009

Many researchers studied cell culturing on surfaces with chemical functional groups. Previously, we reported surface properties of plasma polymerized ethylenediamine (PPEDA) films deposited by plasma enhanced chemical vapor deposition with various plasma conditions. Surface properties of PPEDA films can be controlled by plasma power during deposition. In this work, to analyze correlation of cell adherence/proliferation with surface property, we cultured rat intestinal epithelial cells-18 on the PPEDA films deposited with various plasma powers. It was shown that as plasma power was decreased, density of cells cultured on the PPEDA film surface was increased. Our findings indicate that plasma power changed the amine density of the PPEDA film surface, resulting in density change of cells cultured on the PPEDA film surface.