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최봉규,박희만,강연욱,국영종,Choi, Bong-Kyu,Park, Hie-Man,Kang, Yeon-Wook,Kook, Young-Johng The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.2
흰쥐 해마(hippocampus)에서 acetylcholine(Ach) 유리에 미치는 $A_1-adenosine$ 수용체의 역할과 post-receptor 기전에 있어서 adenylate cyclase 계의 관여여부에 관한 지견을 얻고자 하여 $[^3H]-choline$으로 평형시킨 해마 slice를 사용하여 $[^3H]-ACh$ 유리에 미치는 여러가지 약물들의 영향을 관찰하였다. $A_1-adenosine$ 수용체 흥분제인 $N^6-cyclopentyladenosine(CPA,\;0.1{\sim}10\;{\mu}M)$은 전기자극$(3Hz,\;5\;Vcm^{-1},\;2\;ms,\;rectangular\;pulses)$에 의한 $[^3H]-ACh$ 유리를 용량 의존적으로 감소시켰다. $A_1-adenosine$ 수용체 차단제인 8-cyclopentyl-1, 3-dipropylxanthine$(DPCPX,\;1{\sim}10\;{\mu}M)$은 용량 의존적으로 $[^3H]-ACh$ 유리를 증가시켰으며, 이때 기저(basal)유리 또한 증가됨을 관찰할 수 있었고, $2\;{\mu}M$ DPCPX 전처리는 CPA의 효과를 길항하여 CPA에 의한 용량반응곡선을 우측으로 이동시킴을 볼 수 있었다. G protein 억제제인 N-ethylmaleimide$(NEM,\;10\;&\;30\;{\mu}M)$는 그 자체에 의하여 자극에 의한 ACh 유리를 증가시켰으며, 기저유리 또한 증가함을 볼 수 있었다. NEM 전처리에 의하여 CPA의 효과는 완전히 소실되었다. 한편 adenylate cyclase 활성화제인 forskolin$(0.3{\sim}10\;{\mu}M)$은 기저유리에 변함없이 용량의존적인 $[^3H]-ACh$ 유리의 증가를 초래하였으며 $3\;{\mu}M$ forskolin 전처리는 대량$(10\;{\mu}M)$의 CPA의 효과를 제외하고는 CPA의 효과를 억제시킴을 관찰할 수 있었다. 이상의 실험 결과로 흰쥐 해마의 choline 작동성신경의 presynaptic $A_1-adenosine$ heteroreceptor는 ACh 유리에 중요한 역할을 하고 있으며, ACh 유리의 조절에 Gi-단백질을 통한 adenylate cyclase 계의 관여가 확실하다 하겠다. 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.
나덕렬,연병길,강연욱,민경복,이수현,이상숙,이미라,표옥정,박찬병,김선민,배상수,김동현,Na, Duk-L.,Yeon, Byeon-Gil,Kang, Yeon-Wook,Min, Kyung-Bok,Lee, Soo-Hyun,Lee, Sang-Suk,Lee, Mi-Ra,Pyo, Ok-Jung,Park, Chan-Byung,Kim, Sun-Mean,Bae, Sang-S 대한예방의학회 1999 예방의학회지 Vol.32 No.3
Objectives: In Korea, as in most countries, there will be a sharp increase in the number of dementia patients in the near future. However basic data on dementia prevalence, which is important in defining epidemiologic characteristics and in implementing preventive strategy, are limited. This study was conducted to estimate the prevalence rate of dementia in the urban elderly aged 65 or older in Kwangmyung, Korea. Methods: A two phase design was used for case finding and case identification. In phase I, a representative sample aged 65 or older was selected and interviewed by door-to-door survey with a Korean version of the Mini-Mental State Examination (K-MMSE). In phase II, Of the 946 subjects interviewed in phase 1,356 elderly were randomly selected disproportionately according to K-MMSE score. Of these elderly, 223 (61.5%) underwent standardized clinical evaluations, including psychiatric interview, neurological examination, and neuropsychological assessment. Dementia was diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. The diagnosis of Alzheimer's disease (AD) was made by National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and feinted Disorders Association(NINCDS-ADRDA) criteria and vascular dementia (VD) by DSM-IV. Results: The overall weighted prevalence rate of all dementia among Kwangmyung residents aged 65 or older was 12,8%(age-adjusted rate: 13,0%, 95% Confidence Interval[CI]: 10.6-15.3%). Women had much higher prevalence rate than men even when age was controlled(15.9%[95% CI 12.6-19.2%] vs 7.5%[95% CI 4.0-10.4%]), The rates of dementia were 5.2%, 12.2%, 17.0%, and 34.3% for the age groups of 65-69, 70-74, 75-79 and 80 and over, respectively. The rate of AD appeared to be slightly higher than that of VD(5.2% vs 4.8%), though not statistically significant. Most of the cases(69%) were mild dementia according to CDR(<1) in these subjects. Conclusions : These results showed that the prevalence rate of dementia among urban elderly in Korea appears to be higher than those of other Asian countries.