• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.74-82
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• 2020

Alzheimer's disease (AD) is a progressive and most frequently diagnosed neurodegenerative disorder. However, there is still no drug preventing the progress of this disorder. β-Amyrin, an ingredient of the surface wax of tomato fruit and dandelion coffee, is previously reported to ameliorate memory impairment induced by cholinergic dysfunction. Therefore, we tested whether β-amyrin can prevent AD-like pathology. β-Amyrin blocked amyloid β (Aβ)-induced long-term potentiation (LTP) impairment in the hippocampal slices. Moreover, β-amyrin improved Aβ-induced suppression of phosphatidylinositol-3-kinase (PI3K)/Akt signaling. LY294002, a PI3K inhibitor, blocked the effect of β-amyrin on Aβ-induced LTP impairment. In in vivo experiments, we observed that β-amyrin ameliorated object recognition memory deficit in Aβ-injected AD mice model. Moreover, neurogenesis impairments induced by Aβ was improved by β-amyrin treatment. Taken together, β-amyrin might be a good candidate of treatment or supplement for AD patients.

• Archives of Pharmacal Research
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• v.15 no.2
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• pp.115-125
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• 1992

An attempt was made to investigate the effect of TMB-8[3, 4, 5-trimethoxybenzoate-8 (N, N-diethylamino) octyl ester], which is known to be an inhibitor of intracellular $Ca^{2+}$ release, on catecholamines (CA) secretion evoked by Ach, excess $K^+$, DMPP, McN-A-343 and caffeine from the isolated perfused rat adrenal glands and to cleaify its mechanism of action. The pretreatment with a low dose of TMB-8 $(10 \mu{M)}$ for 20 min led to marked inhibition in CA secretion evoked by Ach (5.32 mM), excess K^+$ (56 mM), DMPP $(100\;\mu{M)}$, McN-A-343 $(100 \mu{M)}$ and BAY-K 8644 $(10^{-5}M)$. Caffeine-induced CA secretion was simimlar to that of control only during the first periods (0-3 min) but thereafter maked inhibition in CA secretion evoked by caffeine was observed during the rest periods up to 30 min. The increased moderate concentration of TMB-8 $(30 \;\mu{M)}$ caused the result similar to that of $10 \;\mu{M}$ TMB-8. However, in adrenal glands preloaded with a high dose of TMB-8 $(100\;\mu{M)}$, CA releases evoked by Ach, excess $K^+$, DMPP, McN-A-343 and caffeine were almost completely blocked by the drug. These experimental data demonstrate that TMB-8 may inhibit cholinergic receptor-mediated and also depolarization-dependent Ca secretion, suggenesting that these TMB-8 effects seem to be mediated through inhibiting influx of extracellular calcium into the rat adrenal medullary chromaffin cells as well as reducing the release of calcium from intracellular sources.

• Korean Journal of Biological Psychiatry
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• v.2 no.2
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• pp.205-217
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• 1995

In comparison with tricyclic antidepressants(TCAs), one of the most interesting characteristics of selective serotonin reuptake inhibitors(SSRIs) is its structural differences, reveals different pharmacological properties. The applications at the moment are most effective in clinical applications to depression. The limited result of the research to date on the various applications of SSRIs has not revealed the total potential and applicability of SSRIs. Therefore, attending physicians utilizing SSRIs do not know the full capabilities of the drug on patients and what the patients may reap in terms of benefit from its curing elements. Physicians must first try to understand the full potential of SSRIs and its potential applications for it to be effective on patients. recently, it has been determined that SSRIs and other drugs when administered together may be more effective in the healing process because SSRIs complements and aids in the enhancement and effect of the other drugs. This article is written to give attention to the reader of the pharmacological properties and the clinical use of SSRIs. It is the authors's hope that continuous research on the particular aspects of SSRIs can aid the clinicians in the use of this SSRIs.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.447-456
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• 1994

In order to elucidate the characterization of receptors involved in inestinal motility of Israeli carp, spontaneously contracting Israeli carp intestinal preperations were prepared and mounted in the organ chambers for contraction traicings using a polygraph. Various contractile agonists were treated and their dose-response curves were constructed. $EC_{50}$ values$(pD_2)$ of each agonist on specific receptors, $pA_2$ values of competitive antagonists against some agonists, and $K_1$, values of noncompetitive antagonists against some agonists were analyzed for characterization of receptors related with the intestinal contraction. Results obtained through the experiments were summarized as follows: 1. Acetylcholine(ACh) exhibited biphasic dose-response curves: initial ACh-induced dose dependent contractions were observed in pM levels but followed by decreased response in in-between concentration levels. Dose dependent contractions reappeared in ${\mu}M$ level. The peaks in pM and ${\mu}M$ levels appeared in $10^{-13}M$ and $3{\times}10^{-5}M$, respectvely. 2. Carbachol(CaCh) exhibited dose dependent contractions from $10^{-9}M$ to $10^{-5}M$, and its $pD_2$ values were higher than those of ACh($5.60{\pm}0.11$). ACh and CaCh exhibited equiactive contractions. Nicotine had no effects on contractile responses of Israeli carp intestine. 3. ACh-induced responses were inhibited by atropine($K_1:7{\times}10^{-8}M$), a muscarinic antagonist, in a non-competitive manner. But CaCh-induced responses were inhibited by both antimuscarinic atropine($pA_2:9.52{\pm}0.14$) and selective $M_2$ antagonistic 4-DAMP($pA_2:8.16{\pm}0.09$), in competitive manners. Nicotine receptor antagonistic decamethonium and hexamethonium had no effects on ACh-and CaCh-induced contractions. Therefore, the cholinergic receptor related to intestinal motility of Israeli carp was assumed as $M_2$ type. 4. In Israeli carp intestine, 5-HT (serotonin) exhibited dose dependent contractions in concentration range from $10^{-8}M$ to $10^{-5}M$. The maximal responses, however, were corresponded to about 50% of those of ACh or CaCh. 5-HT induced contractions were inhibited by $5-HT_2$ antagonistic ketanserin ($K_1: 7.8{\times}10^{-4}M$) in a non-competitive manner, but not by both of anti $5-HT_1$, spiperone and anti $5-HT_3$, MDL-72222. Hence, $5-HT_2$ receptors are suggested to be existed in Isreli carp intestine.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.83-94
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• 1998

Objectives : Phencyclidine(PCP) or PCP-like substances such as ketamine have been known to rekindle the cognitive dysfunction in schizophrenia. The aims of this study were to identify whether PCP-like substances can produce cognitive deficit in schizophrenia, to discuss relation with aging process, and finally to speculate underlying neurochemical mecha-nisms by various drug responses. Methods : In experiment I, radial maze tests were done in 24 Sprague-Dawley rats for 3 days to get baseline data. Being divided into 4 groups(6 rats respectively) of normal aged, normal adult controls, atropine-treated and ketamine-treated, the radial maze tests were repeated on every week for 6 weeks, and then the rats were sacrificed by intracardiac perfusion with phosphate-buffered 10% formaldehyde solution for histology. The brain specimen was stained with hematoxylin-eosin to count cells in the prefrontal cortex and hippocampus. In experiment II, radial maze tests were done for 48 rats before any drug treatment and only after ketamine administration. Thereafter, haloperidol, bromocriptine, clonidine, nimodipine, tacrine, valproic acid, naloxone and fluoxetine were intramuscularly injected on every other day in addition to ketamine. Radial maze tests were repeated on every week for 6 weeks, and then rats were prepared by the same procedure for histology. Results : 1) Reaction times of radial maze tests of atropine-treated rats were significantly prolonged than those of normal aged(p<0.05) or normal adult controls(p<0.05). Cell numbers of prefrontal cortex & hippocampus in ketamine-treated rats were significantly reduced than those in normal aged (p<0.05) or normal adult controls(p<0.005). 2) Reduced cell numbers by ketamine became significantly raised by tacrine administration in prefrontal cortex & hippocampus(p<0.05), while there were no significant changes on radial maze tests. Cell numbers also tended to be raised by nimodipine, fluoxetine and haloperidol administration. Conclusions : In conclusion, the visuospatial memory disorders in ketamine-induced psychotic rats might be partly asso-ciated with aging process. Furthermore, the responses to the various drugs suggested cholinergic system might have an important role in the neurochemical mechanism of the cognitive dysfunction in ketamine-induced psychosis. Otherwise, calcium metabolism as well as serotonergic and dopaminergic systems seemed to be possibly related.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.87-100
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• 1994

It has been known for some time that dopamine-containing cells are existed in sympathetic ganglia, i.e., small, intensely fluorescent cells. However, its role and mechanism of action as a peripheral neurotransmitter are poorly understood so far. In the present study, an attempt was made to examine the effect of apomorphine, which is known to be a selective agonist of dopaminergic $D_2$. receptor on secretion of catecholamines (CA) from the isolated perfused rat adrenal gland. The perfusion of a low concentration of 10uM apomorphine into an adrenal vein for 20 min produced significant reduction in CA secretion induced by 5.32 mM ACh, 56 mM KCl, 100 uM DMPP and 100 uM McN-A-343. Increasing apomorphine concentration to 30 uM led to more markedly decreased CA secretion as compared to the case of 10 uM apomorphine and also did inhibit clearly CA release by $10^{-5}M$ Bay-K-8644. Furthermore, in adrenal glands preloaded with a higher dose of 100 uM apomorphine, CA releases evoked by ACh, excess $K^+$, DMPP and McN-A-343 were almost abolished by the drug. The perfusion of $3.3{\pm}10^{-5}M$ metoclopramide, which is well-known as a selective dopaminergic $D_2$ antagonist, produced significantly inhibitory effect of CA release by ACh, DMPP and McN-A-343 but did not affect that by excess $K^+$. However, preloading of 30uM apomorphine in the presence of metoclopramide did not modify the CA secretory effect of excess $K+$ and DMPP. These experimental results demonstrate that apomorphine causes dose-dependent inhibition of CA secretion by cholinergic receptor stimulation and also by membrane depolarization from the isolated perfused rat adrenal gland, suggesting that these effects appear to be exerted by inhibiting influx of extracellular calcium into the rat adrenal medullary chromaffin cells through activation of inhibitory dopaminergic receptors.

• Journal of Yeungnam Medical Science
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• v.11 no.2
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• pp.293-302
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• 1994

The objective of this study was to establish a good methodology to isolate single smooth muscle cells that are alive and respond properly to pharmacological agents. Canine urinary bladders were employed as the source of single cells, and acetylcholine, atropine and imipramine were used as indicators of pharmacological responsiveness. Imipramine, an antidepressant drug exhibited the anticholinergic and calcium antagonizing properties on rat detrusor muscle. To establish a control value for a further experiment to elucidate the mechanism of action of imipramine on detrusor muscle, we measured the concentration-response of single cells to acetylcholine in the presesnce of imipramine by length of the cells and compared the result with the response in the presence of atropine. Tiny chops of smooth muscle taken from anesthetized canine urinary bladder were incubated in collagenase solution at $36^{\circ}C$ for 17-20 minutes. The collagenase solution included collagenase 1.2 mg/ml, soybean tryspin inhibitor 0.08 mg/ml, bovine serum albumin 2% in 10 ml Krebs-Henseleit buffer solution aerated with a consistent breeze of 95/5% $O_2/CO_2$, to maintain the pH at 7.4. After washing with plain K-H solution on 450 mesh, cells were dissociated from the digested tissue for 12-15 minutes. Cell suspension was transfered in 5 ml test tubes and acetylcholine was added for the final concentration to be $10^{-14}M{\sim}10^{-9}M$. To find the optimal time to fix the cells to determine the contractile responses, 1% acrolein was added 5, 10, 20, 30, 60 and 120 seconds after the administration of ACh. The length of cells fixed by acrolein were measured by microscaler via CCTV camera on phaes-contrast microscope. The average length of 50 cells from a slide glass was taken as the value of a sample at the very concentration point. Single cells were isolated from canine detrusor. The length of untreated cells varied from 82 ${\mu}m$ to 94 ${\mu}m$. The maximal response to actylcholine $10^{-9}M$ was accomplished within 5 seconds of exposure, and the shortening was $19{\pm}3$%. Atropine reduced the contraction of the cells concentration-dependently. Imipramine which exerts a cholinergic blocking action on some smooth muscles also reduced the contraction concentration-dependently and by a similar pattern as atropine. These findings document that imipramine may exerts a cholinergic blocking activity in the single smooth muscle cells isolated from canine urinary bladder.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.25 no.1
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• pp.55-74
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• 2012

Objective : The purpose of this study is to investigate the skin disease in Sanghanron"傷寒論" and Geumgweyoryak"金匱要略". Methods : We conducted a study on the original text paragraphs of Sanghanron and Geumgweyoryak containing the skin disease and analysis of Woo, Oh, Sung, Zhang, etc. We drew a parallel between skin disease from Sanghanron and Geumgweyoryak and matching diagnoses from western medicine. Results : The results were as follows. 1. In Sanghanron and Geumgweyoryak pruritus was related to psychogenic pruritus and similar to skin disease caused by decrease of sweating, dry skin in cholinergic urticaria, atopic dermatitis and eczema, etc. in western medicine. 2. In Geumgweyoryak ichthyosis was caused by woman's disease, after menopause, chronic disease and malnutrition and related to winter itch and xerotic eczema in western medicine. 3. In Sanghanron Goose bumps, keratosis follicularis, acute and chronic urticaria and cold urticaria were occurred because of poorly managed fever care and side effect of antibiotic. 4. In Geumgweyoryak red face was similar to face flushing and side effects, which is after drug and laser treatment on face, in western medicine. 5. In Geumgweyoryak urticaria was, in a broad sense, skin disease with pruritus and secondary infection resulted from scratch. Skin diseases with pruritus are similar to urticaria, dermatitis herpetiformis, lichen planus, atopic dermatitis, contact dermatitis, psoriasis, nummular eczema, lichen simplex chronicus, prurigo nodularis, neurodermatitis and internal disease with pruritus in western medicine. 6. In Geumgweyoryak spots in the skin were caused by fever and similar to allergic purpura and SLE symptom in western medicine. 7. In Geumgweyoryak bullous disease with yellowish discharge was similar to eczema, pustule, atopic eczema, etc. in western medicine. 8. In Geumgweyoryak repeated inflammation of oral cavity, genitals, eyes and skin was similar to Behcet's disease in western medicine. 9. In Sanghanron and Geumgweyoryak boil was similar to abscess and acute lymphadenitis in western medicine caused by oily foods and infections. 10. In Geumgweyoryak swelling and boil were occurred in a poor health. Damage from metalic material could cause a convulsion and was similar to tetanus in western medicine. Conclusion : We analyzed the original text paragraphs of Sanghanron and Geumgweyoryak and explanations about skin disease. As a results, we found out etiology, pathogenesis, treatments of the skin disease in Sanghanron and Geumgweyoryak. Further we compared with western medicine to develop better understanding of the skin disease.

• Applied Microscopy
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• v.24 no.3
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• pp.23-33
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• 1994

It is well known that dichlorvos (DDVP), an organophosphate insecticide in common use, is so easily and rapidly hydrolyzed and excreted that it has usually little toxic effect on human body. In these days, however, it is widely used as an industrial and domestic insecticide and as an anthelmintic agent for animals, so that the accident of chemical poisoning occurs frequently. DDVP acts as a powerful inhibitor of carboxylic esterase, which can cause accumulation of acetylcholine at the synapses so paralysis of muscle and the transmission failure in cholinergic synapses dueing to desensitization of acetylcholin receptor may occure. Moreover accumulation of the acetylcholine brings about the elevation of the cyclic-AMP, which alters the cellular metabolisms of nucleic acid, carbohydrate, protein and lipid. Present study has undertaken to investigate the cardiotoxic effect of DDVP by electron microscopic study. A total of 30 Sprague-Dawley strain rats, weighing about 250gm were used as experimental animals. 2mg/kg/day of DDVP is intraperitonealy injected 3 times with intervals of every other day. On 1 day, 3 days, 5 days, 7 days and 14 days after drug administration, the animals were sacrified by cervical dislocation. Left ventricular cardiac muscles were resected and sliced into $1mm^3$. The specimens were embedded with Epon 812 and prepared by routine methods for electron microscopical observation. All preparations were stained with lead citrate and uranyl acetate and then observed with Hitachi-600 transmission electron microscope. The results were as follows: 1. In the cardiac muscle of DDVP treated rats, mitochondria with disorganized double membrane and mitochondrial crista, and vacuole formation in mitochondrial matrix were observed. But structures of mitochondria were recovered to normal in 14 days group. 2. In the cardiac muscle of DDVP treated rats, cisternae of sarcoplasmic reticulum were dilated and sacculated. But these changes were recovered to normal in 14 days group. 3. In the cardiac muscle of DDVP treated rats, glycogen particles around damaged myofibrils were decreased. But amount of glycogen particles were restored in 14 days group. 4. In the cardiac muscle of DDVP treated rats, disruption and discontinuation of myofilaments and disorganization of Z-disc were observed. But the structures of myofibrils were recovered to normal in 14 days group. It is consequently suggested that DDVP would induce the reversible degenerative changes on the ultrastructures in cardiac muscle of rat.

• Journal of Yeungnam Medical Science
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• v.6 no.2
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• pp.207-215
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• 1989

The authors studied ED50 of bethanechol on the contractilities of the smooth muscles isolated from various organs of rat under the presence of atropine(a classical competitive blocker of cholinergic muscarinic receptor) or minaprine(a newly developed antidepressant drug) to investigate the pheripheral anticholinergic effect of minaprine. The results were as follows ; 1) There was no significant difference between ED50 of bethanechol in the control group and that under the presence of minaprine $10^{-8}M$ and $10^{-7}M$ in the smooth muscles isolated from the duodenum. 2) There was no significant difference between ED50 of bethanechol in the control group and that under the presence of minaprine $10^{-8}M$ and $10^{-7}M$ in the smooth muscles isolated from the ascending colon. 3) There was significant difference between ED50 of bethanechol in the control group and that under the presence of minaprine $10^{-8}M$ and $10^{-7}M$ in the smooth muscles isolated from the urinary bladder(P<0.01). 4) There was significant difference between ED50 of the atropine $10^{-8}M$ and minaprine ($10^{-8}M$) in the smooth muscles isolated from the urinary bladder(P<0.05).