• Journal of Korean Neurosurgical Society
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• v.66 no.4
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• pp.446-455
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• 2023

Objective : Chronic subdural hematoma (CSDH) is a common neurosurgical disease and generally treated with burr-hole surgery alone. Tranexamic acid (TXA) is an antifibrinolytic agent that potentially reduces recurrence rates and the residual hematoma volume. However, the role of postoperative TXA medication remains unclear to date. This study aimed to verify the effectiveness of adjunctive TXA in the view of early hematoma resolution. Methods : Between January 2018 and September 2021, patients with CSDH who underwent burr-hole trephination in a single tertiary institute were reviewed. The study population was divided into three groups, TXA, non-TXA, and antithrombotics (AT) groups, according to the medical history of cardio-cerebrovascular disease and TXA administration. The primary endpoint was CSDH recurrence, defined as re-appearance or re-accumulation of CSDH requiring neurosurgical interventions. The secondary outcome was CSDH resolution, defined as complete or near-complete resorption of the CSDH. The CSDH resolution time and serial changes of hematoma thickness were also investigated. Results : A total of 240 patients was included in the analysis consisting of 185 male and 55 female, with a median age of 74 years. During the median imaging follow-up period of 75 days, 222 patients were reached to the primary or secondary endpoint. TXA was administered as an adjunctive therapy in 41 patients (TXA group, 16.9%) while 114 patients were included in the non-TXA group (47.9%) and 85 were in the AT group. The recurrence rate was the lowest in the TXA group (2.4%), followed by non-TXA (7.0%) and AT (8.2%) groups. However, there was no statistical significance due to the small number of patients with recurrence. CSDH resolution was achieved in 206 patients, and the median estimated time to resolution was significantly faster in the TXA group (p<0.001). Adjunctive TXA administration was a significant positive factor for achieving CSDH resolution (p<0.001). The hematoma thickness was comparable among the three groups at the initial time and after surgery. However, CSDH thickness in the TXA group decreased abruptly in a month and showed a significant difference from that in the other groups (p<0.001). There was no TXA-related adverse event. Conclusion : The adjunctive use of TXA after CSDH surgery significantly facilitated the resorption of residual CSDH and resulted in the early CSDH resolution. Adjunctive TXA may be an effective treatment option to reduce recurrence by enhancing CSDH resolution in the selective patients.

• The Journal of Korean Society of Virology
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• v.27 no.2
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• pp.227-237
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• 1997

In order to search for anti-Herpes simplex virus (HSV) type-1 agents from Korean medicinal herbs and Korean traditional prescriptions (herb complexes), we selected 80 medicinal herbs and 45 prescriptions, based on a review of the Korean traditional medicine books. Both methanol extracts and boiling-water extracts were tested by means of the MTT assay (tetrazolium based colorimetric assay). Ten of the 125 methanol extracts: CM-11, CM-18, CM-19, CM-21, CM-22, CM-39, MM-3, MM-18, MM-29, MM-73 (see explanation of nomenclature below), showed efficacy against HSV-1. Twelve of the water extracts: CW-2, CW-3-I, CW-3-II, CW-18, MW-3, MW-5 MW-6, MW-12, MW-47, MW-69, MW-73 and MW-79 were active. #3 (individual herb) and #73 (individual herb) were interesting because both water and methanol extracts were active. Especially, #3 is a part of composition of Hong-il-$laksamd{\check{u}}ngbang$ and Hojanghaedokt'ang which have anti-HSV-1 activitives. The SI value of MW-69 and CW-18 was relative high as $10.2{\pm}0.7$ and $11.8{\pm}2.2$. The cytotoxic effect on Vera cells of $Panch'{\check{o}}nch'onch'{\check{o}}ngbang$, Taraxacum platycarpum H. Dahlst. and acycloguanosine was determined by MTT assay. Water extracts of $Panch'{\check{o}}nch'onch'{\check{o}}ngbang$ (prescription) and Taraxacum platycarpum H. Dahlst. showed very weak cytotoxic effects on Vero cells at > $100\;{\mu}g/ml$ but acycloguanosine showed strang cytotoxic effects on Vera cells at > $100\;{\mu}g/ml$. As a result, #3, #73, MW-69 and CW-18 are considered as potentially useful for anti-HSV-1 agent and will be the focus of further research. Abbreviations: CM - methanol extracts of traditional prescriptions; CW - water extracts of traditional prescriptions; MM - methanol extracts of individual herbs; MW - water extracts of individual herbs.

• Journal of Life Science
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• v.16 no.2 s.75
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• pp.289-296
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• 2006

In order to establish highly efficient gene transfer condition at early stage of soybean transformation, various experiments were performed and compared their efficiencies by transient GUS analysis; those conditions are genotype determination of Korean soybean cultivars for amenability to Agro-infection, appropriate agar and selective agent concentration, orientation of explant placement, hormone pre-culture, and liquid selection condition. In the genotype screen of Korean soybean varieties, 14 amenable genotypes were selected. For efficient Agrobacterium washing, cefotaxime was chosen and hygromycin at the concentration of 10 and 15 ppm was used as selection agent in the media. Agar concentration was slightly better in 0.6% and 0.8% for both shoot and callus formation, and explant placement with adaxial side down showed high frequency of GUS expression. For wounding treatment, oriental needle was efficient than scalpel for shoot formation and gene transfer. To increase the frequency of gene transfer, hormone pre-treatment was applied. BA at the concentration of 5 and 10 ppm resulted in better survival at the late stage of selection in shoot elongation media. Selection in liquid media after hormone pre-treatment seemed to be effective to remove the escaped non-transformants at early stage of procedure. Considering the results obtained, Eunhakong could be the first choice as a material for soybean transformation among Korean soybean genotypes.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.77-90
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• 2004

Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

• Resources Recycling
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• v.31 no.1
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• pp.65-77
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• 2022

A study was conducted in Korea on the leaching behavior and possibility of recovery of vanadium and other valuable metals from domestic vanadium titanomagnetite (VTM) by direct acid leaching. In this study, a VTM concentrate containing 0.8% V₂O₅ was used, and the ratio of magnetite to ilmenite was calculated as 1.9:1 by using the HSC program. The leaching behavior of vanadium from the VTM was similar to that of iron, and it was affected by the concentration of sulfuric acid and temperature. Further, titanium could be leached in the form of TiOSO₄ at a temperature higher than 75℃. To improve the leaching efficiency of V, Fe, and Ti in VTM, reductive sulfuric acid and oxidative sulfuric acid leaching were performed. When Na₂SO₃ was used as a reducing agent, the leaching rate of vanadium was 80% of that in that case of leaching by sulfuric acid. Similarly, the leaching rate of titanium increased from 20% to 50%. When Na₂S₂O₈ was used as an oxidation agent, most of the vanadium was leached, and the main residue found by XRD analysis was ilmenite. In studies on the possibility of recovering valuable metals, the selective extraction of metals is hardly achieved by solvent extraction from oxidation leaching solutions; however, in this study, Cyanex 923, a solvation extractant from reductive leaching solutions, could selectively extract Ti.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.302-313
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• 1995

Background: Tumor necrosis factor(TNF) showed antitumor cytolytic effects on sensitive tumor cells in numerous in vivo and in vitro studies. But it could not be administered systemically to human because of severe systemic adverse effects at effective concentrations against tumor cells. Many studies showed that a high concentrations of TNF in the local milieu may evoke in vivo TNF-responsive mechanisms sufficient to suppress tumor growth. Recently developed technique of TNF gene transfer to tumor cells using retrovirus vector could be a good candidate for local TNF administration. TNF is also known to synergistically enhance in vitro cytotoxicity of chemotherapeutic drugs targeted to DNA topoisomerase II against TNF-sensitive tumor cell lines. In this study the in vitro chemosensitivity against DNA topoisomerase II targeted chemotherapeutic drugs was evaluated using some respiratory cancer cell lines to which TNF gene had been transferred. Method: NCI-H2058, a human mesothelioma cell line, A549, a human lung adenocarcinoma cell line and WEHI 164 cell line, a murine fibrosarcoma cell line were treated with etoposide and doxorubicin, which are typical topoisomerase II - targeted chemotherapeutic agents, at different concentration. The resultant cytotoxicity was measured by MIT assay. Then the cytotoxicity of the same chemotherapeutic agents was measured after TNF-$\alpha$ gene-transfer and the two results were compared. Results: The cytotoxicity was not increased significantly in WEHI164 cell line and A549 cell line but statistically significant increase was observed in H2058 cell line when TNF-$\alpha$ gene was transferred(p<0.05). Conclusion: These findings show that TNF-$\alpha$ gene transfer to respiratory cancer cell lines results in variable effects on chemosensitivity against topoisomerase II inhibitor among different cell lines in vitro and can be additively cytotoxic in certain selective tumor cell lines.

• The Journal of the Korean Society for Microbiology
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• v.15 no.1
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• pp.19-32
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• 1980

Besides the benefits of antimicrobial agents in the control of various infectious diseases, widespread and prolonged use of particular antimicrobial agents has brought about the increase of drug-resistant strains in a community and the profound changes in the pattern of infectious diseases. In Korea, there are some remote villages where no clinics and drug stores are available and the residents in those areas are assumed to have fewer chances to contact with antimicrobial agents. In the present study, the differences in susceptibilities to 14 antimicrobial agents between the isolates from rural areas(R) and Seoul National University Hospital(SNUH, H) were studied. The isolates and their numbers were Staphylococcus aureus, R;55, H;68), Enterococci(R;28, H;30), Escherichia coli(R;40, H;40), Enterobacter aerogenes(R;25, H;21) and Klebsiella pneunoniae(R;58, H;67). Minimal inhibitory concentrations(MIC's) of penicillin, ampicillin, carbenicillin, cephalexin, tetracycline, oxytetracyline, doxycycline, minocycline, gentamicin, kanamycin, streptomycin, erythromycin, troleandomycin and co-trimoxazole were determined by agar dilution method. I. Comparison of MIC's and resistant strain proportions between isolates from SNUH and rural areas. MIC's and/or resistant strain proportions of the isolates from SNUH were significantly higher than those of the isolates from rural areas in the cases of 1. S. aureus to doxycycline, streptomycin and kanamycin. 2. E. coli to penicillin, ampicillin, carbenicillin, tetracycline, oxytetracycline, doxycycline, minocycline, streptomycin, kanamycin, erythromycin and co-trimoxazole. 3. E. aerogences to carbenicillin, tetracycline, oxytetracycline, doxycycline, minocycline, streptomycin, kanamycin, genaamicin and co-trimoxazole. 4. K pneunoniae to penicillin, ampicillin, tetracycline, oxytetracycline, doxycycline, monocycline, streptomycin, kanamycine, gentamicin and co-trimoxazole. However, the mean MIC and resistant strain proportion of S. aureus to tetracycline were higher in isolates from rural areas than in those from SNUH and Enterococci showed no differences in susceptibilities to the antimicrobial agents between isolates from rural areas and from SNUH. Therefore, in general, differenes in susceptibility to these antimicrobial agents between the isolates from rural areas and SNUH were remarkably greater and broader in gram negative enteric bacteria. II. Multiple drug resistance pattern. Patterns and incidences of multiple drug resistance were studied with penicillin, ampicillin, tetracycline, cephalexin, gentamicin, streptomcin, kanamycin and co-trimoxazole in Enterococci, E. coli, E. aeroges and K. pneumoniae. There appeared significant differences in the incidence of multiply drug-resistant strains and multiple drug resistance patterns between the isolates from SNUH and rural areas in Enterococci, E. coli, E. aerogenes and K. pneumoniae. However, there was no difference in the incidence of multiply drug-resistant strains between isolates of S. aureus from SNUH and rural areas but the pattern of multiple resistance of the SNUH strains of S. aureus was diverse, while that of the rural strains was predominantly confined to penicillin-tetracycline combination. The incidence of multigly drug-resistant strains and diversity of their patterns were the highest in E. coli strains isolated from SNUH and there were no multiply drug resistant strrains in Enterococci and K. pneumoniae strains isolated from rural areas. The number of drug-resistance determinants was also different between the isolates from rural areas and SNUH. Most of the multiply drug-resistant strains of E. coli, E. aerogenes and K. pneumoniae isolated from SNUH were resistant to more than 3 kinds of antimicrobial agents, most frequently to ampicillin, tetracycline and streptomycin, while multiply drug-resistant strains from rural areas were resistant to 2 kinds of antimicrobial agents among ampicillin, tetracycline and streptomycin. With drug-resistant E. coli strains, resistance to tetracycline which was used most widely since 1951 was most frequently involved as a part of mutliple drug-resistance, followed by resistance to ampicillin and streptomycin. This strongly suggests that emergence of drug-restant strains in a community is directly dependent on the selective pressure exerted by the antimicrobial agent used. III. Cross resistance. Cross resistance of bacteria was studied among tetracycline penicillin, aminoglycoside and macrolide derivatives by analyzing correlation coefficients of sucseptibilities using the least square method. In this study, there were high correlations among the susceptibilities to related derivatives. It appears that the relatively low correlations in susceptibilities present in some cases are due to intrinsic resistance of E. aerogenes to penicillin, Enterococci to aminoglycoside and E. coli E. aerogenes and K. pneumoniae to macrolide derivatives.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.240-245
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• 1999

Object : This study was designed to evaluate the effects of olanzapine on the schedule-induced polydipsia(SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered olanzapine as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol for the dopamine antagonist to rats which showed schedule-induced polydipsic behavior. Methods : Spraque-Dawley rats weighing 200-250gm were individually housed and maintained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds(FT-60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior(greater than 3 times of water per session on average). 5 groups of rats were administered olanzapine(3mg/kg, i.p), olanzapine(10mg/kg, i.p), fluoxetine(5mg/kg, i.p.), haloperidol(0.1mg/kg, i.p.), and vehicle(1cc/kg, i.p.) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a posthoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats(N=8) were individually housed and given a single bolus(14.5gm) of food per day which maintained them at their average body weight. Results and Conclusion : The results were as follows ; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake over the 3 weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 3mg group showed significant decrease in the amount of water intake at 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 10mg group showed significant decrease in the amount of water intake at 2nd and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their average amount of polydipsic water intakes. 3) The fluoxetine group showed significantly lower amounts of water intake than the haloperidol group at 2nd weeks of drug treatment. And also the fluoxetine group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. The olanzapine 3mg group and the olanzapine 10mg group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. Above findings suggest that the fixed time feeding procedure for schedule-induced polydipsia as an animal model of obsessive compulsive disorder was effective to the evaluation of pharmacological challenge study. The authors assume that the serotonin hypothesis and the serotonin-dopamine interaction hypothesis are preferred to the dopamine hypothesis in the biological etiology of obsessive-compulsive disorder.

• Development and Reproduction
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• v.13 no.2
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• pp.105-114
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• 2009

Ethane 1,2-dimethane sulfonate (EDS) is a well-known alkylating agent used as selective Leydig cell (LC) toxicant to create a testicular dysfunction model. Previous studies including our own clearly demonstrated the dramatic weight loss of the androgen dependent accessory sex organs such as epididymis, seminal vesicle and prostate gland in this 'LC knock-out' rats. The present study was performed to evaluate the effect of EDS administration on histological changes of the epididymis, seminal vesicle and prostate in adult rats. Adult male Sprague-Dawley rats (350$\sim$400 g B.W.) were injected with a single dose of EDS (75 mg/kg, i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. Tissue weights (testis, epididymis, seminal vesicle and prostate gland) were measured. The histological changes of tissue were observed by a light microscopy using hematoxylin & eosin staining. Weights of the reproductive and accessory organs progressively declined after the EDS treatments (weeks 1, 2 and 3). After this, the decrease was stopped, then gradually returned to the normal levels. There was a partial (about 60%) recovery of the epididymis weight during weeks $6{\sim}7$. The cross section of epididymis revealed an increase in thickness of the epithelium during weeks $1{\sim}3$. In contrast, considerable reduction of epithelial thickness in seminal vesicle was observed during same period. Similarly, a reduction in thickness of prostate epithelial layer was found during weeks $1{\sim}3$, then it was back to normal thickness after week 4. Taken together, the present study demonstrated that the temporally induced androgen-deficiency by EDS treatment could result the prominent alterations in histology of the accessory sex organs. Further studies on the physiological and molecular regulation of these androgen-sensitive organs using EDS model will be helpful to understand the normal and pathological development and differentiation mechanism of these organs.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.129-136
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• 1992

As it has been reported that the depolarization-induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus and various lines of evidence indicate the involvement of adenylate cyclase system in $A_1-adenosine$ post-receptor mechanism in hippocampus, it was attempted to delineate the role of adenylate cyclase system in the $A_1-receptor-mediated$ control of ACh release in this study. Slices from rat hippocampus were incubated with $[^3H]-choline$ and the release of the labelled products was evoked by electrical stimulation $(3\;Hz,\;5\;Vcm^{-1},\;2\;ms,\;rectangular\;pulses)$, and the influence of various agents on the evoked tritium-outflow was investigated. $N^6-cyclopentyladenosine$ (CPA), a specific $A_1-adenosine$ receptor agonist, in concentrations ranging from 0.1 to $10\;{\mu}M$, decreased the $[^3H]-ACh$ release in a dose-dependent manner without the changes of basal rate of release. 8-cyclopentyl-1,3-dipropylxanthine $(DPCPX,\;1{\sim}10\;{\mu}M)$, a selective $A_1-receptor$ antagonist, increased the $[^3H]-ACh$ release in a dose-related fashion with slight increase of basal tritium-release. And the CPA effects were significantly inhibited by DPCPX $(2\;{\mu}M)$ pretreatment and the dose-response curve produced by CPA was shifted to the right. The responses to N-ethylmaleimide $(NEM,\;10\;&\;30\;{\mu}M)$, a SH-alkylating agent of G-protein, were characterized by increments of the evoked ACh-release and the basal release, and the CPA effect were completely abolished by NEM pretreatment. Forskolin, a specific adenylate cyclase activator, in concentrations ranging from 0.3 to $10\;{\mu}M$, increased the evoked ACh-release in a dose-dependent manner and the CPA effects were inhibited by forskolin. These results indicate that the $A_1-adenosine$ heteroreceptor plays an important role in ACh-release via nucleotide-binding protein Gi in the rat hippocampus and that the adenylate cyclase system might be participated in this process.