초등학교 저학년 단위학습공간의 유형 및 특성 분석

양완숙,정상규,박우장,이훈 대한건축학회지회연합회 2002 대한건축학회연합논문집 Vol.4 No.4

Inverse Agonists at $A_1$ Adenosine Receptors in Rat Cerebral Cortex

박경선,양완숙,김경환,Park, Kyung-Sun,Yang, Wan-Suk,Kim, Kyung-Hwan The Korean Society of Pharmacology 1996 대한약리학잡지 Vol.32 No.1

전통적인 수용체 이론에 따르면 상경적 길항제는 효현제와 수용체의 같은 부위에 작용하지만, 효능(efficacy)이 없기 때문에 생물학적 반응을 일으키지는 않는다. 그러나 최근에 발표되는 자료들에 따르면 모든 길항체의 효능(efficacy)이 0가 아니라 음수도 될 수가 있다고 생각된다. 이러한 음수의 효능을 갖는 약물을 역효현제라 부른다. 본 연구에서는 쥐의 cerebral cortex에서 얻은 membranes을 사용하여, $A_1$ 아데노신 수용체에 작용하는 역효현제를 인구하였다. 8개의 길항제로 알려진 약물들이 G단백에 대한 $[^{35}S]GTP_{\gamma}S$ 결합을 감소시키는 정도를 측정함으로써 역효현제의 특성을 검색하였다. 효현제에 의한 $[^{35}S]GTP_{\gamma}S$ 결합의 증가는 이틀 길항제틀에 의해 완전히 억제되었지만, 검색한 8개의 길항제는 두 군으로 구분되었다. DPCPX를 포함한 7개 길항제는 효현제 부재시의 basal $[^{35}S]GTP_{\gamma}S$ binding을 통계적으로 의의있게 감소시켜 역효현제의 특성을 나타내는 반면, CCS-15943은 basal $[^{35}S]GTP_{\gamma}S$ binding에 아무런 영향을 주지 않았다. NEM을 membranes에 처치하면 PIA에 의한 $[^{35}S]GTP_{\gamma}S$ binding이나 basal binding 둘다 감소하는데 이는 $[^{35}S]GTP_{\gamma}S$ binding의 상당부분이 G단백의 activated state를 나타내는 것을 알 수 있다. 또한 $[^3H]DPCPX$를 이용한 competitive binding assay에서 0.1 mM GTP는 효현제인 PIA의 apparent affinity를 감소시켰으며, DPCPX의 apparent affinity는 증가시키고, CGS-15943에는 아무런 영향을 미치지 않았다. 이것은 상기의 $[^{35}S]GTP_{\gamma}S$ binding의 결과를 뒤받침해 주는 결과라고 생각된다. According to the traditional receptor model, competitive antagonists share with agonists the ability to bind to a common site on receptors, but they are different from agonist in that they cannot trigger the biological response-i.e., they lack intrinsic efficacy. Recent findings extend the model by indicating that not all antagonists display an intrinsic efficacy of zero but that some display 'inverse agonism'. In the present study we studied the inverse agonism at $A_1$ adenosine receptors in membranes prepared from rat cerebral cortex. Eight commercially available $A_1$ adenosine receptor antagonists (CGS-15943, ADPX, CPT, DPCPX, DPX, N-0840, PACPX and 8-PT) were screened for inverse agonism by measuring the extent of $[^{35}S]guanosine-5'-({\gamma}-thio)$ triphosphate $([^{35}S]GTP_{\gamma}S)$ binding to G proteins. The agonist-induced stimulation of $[^{35}S]GTP_{\gamma}S$ bindings was completely blocked in the presence of $A_1$ adenosine receptor antagonists. Under optimal conditions, two types of antagonists could be distinguished. Seven antagonists including DPCPX decreased the basal $[^{35}S]GTP_{\gamma}S$ binding in the absence of agonist, displaying inverse agonist activity. One (CGS-15943) had no effect on the basal bindings. N-ethylmaleimide treatment reduced the basal bindings as well as agonist-mediated stimulation of $[^{35}S]GTP_{\gamma}S$ bindings, indicating that a substantial amount of this binding reflects an activated state of the C proteins. In good agreement with these findings, 0.1 mM GTP decreased the apparent affinity of the receptors for the agonist PIA, increased that for DPCPX, and had no effect on that for CGS-15943.

흰쥐 대뇌피질에서 $A_1$ 아데노신 수용체의 탈감작

박경선,양완숙,김경환,Park, Kyung-Sun,Yang, Wan-Suk,Kim, Kyung-Hwan 대한약리학회 1996 대한약리학잡지 Vol.32 No.2

Following the subcutaneous administration of $R(-)N^6-(2-phenylisopropyl)adenosine(600\;nmol/kg/hr)$ to rats for 1 week using t$Alzet^{\circledR}$ mini-osmotic pumps, $A_1$ adenosine receptor functions were determined using $[^3H]DPCPX$ binding, $[^{35}S]GTP_{\gamma}S$ binding, and adenylyl cyclase assays. $A_1$ adenosine receptor binding and the inhibition of adenylyl cyclase activity by PIA was not altered in cerebrocortical membranes prepared from PIA-treated rats. However, there was a significant decrease in the $A_1$ adenosine receptor-mediated stimulation of $[^{35}S]GTP_{\gamma}S$ binding to cerebrocortical membranes prepared from PIA-treated rats(22.0% decrease in basal activity; 19.7% decrease in maximal activity). These results suggest that the desensitization of $A_1$ adenosine receptors following chronic administration involves agonist-induced uncoupling of the receptors from G proteins rather than alteration of $A_1$ adenosine receptor molecules. It is also suggested that the determination of stimulation of $[^{35}S]GTP_{\gamma}S$ binding to G proteins is a suitable tool in studying the receptor regulation including desensitization

김치 발효를 위한 Leuconostoc mesenteroides 균주의 개량과 starter로의 첨가효과

강상모,양완숙,김영찬,정은영,한용구 한국산업미생물학회 1995 한국미생물·생명공학회지 Vol.23 No.4

김치로부터 Leuconostoc mesenteroides 균주를 선별한 후, NTG로 변이처리를 하여 내산성이며, 낮은 pH에서도 증식하며, 높은 CO_2 생성 능력을 갖는 균주로 개량하였다. HCl로 pH를 조절한 MRS 배지에서 변이주 M-10균주는 30℃에서 pH 5.0∼3.5, 20℃에서는 pH 5.0∼3.8, 10℃에서 변이주 M-10균주가 야생주 K-1균주 보다 더 많은 CO_2를 생성하였다. 젖산으로 pH를 조절한 MRS배지에서 내산성 변이주 Leuconostoc mesenteroides M-10균주가 받는 증식저해 영향은 야생주 K-1균주에 대한 것보다 적었다. 내산성 변이주 Leuconostoc mesenteroides M-10균주를 김치에 starter로 첨가하였을 때 10℃에서 야생주 K-1균주에 비하여 당소비가 떨어지고 pH 변화량과, 총산도 증가폭도 감소하고, 상쾌미에 의한 기호도도 향상되는 것이 나타났다. The heterofermentative Leuconostoc mesenteroides, which is propagated form the initial to the intermediate stage of Kimchi fermentation, produces organic acids and carbon dioxide to impart refreshment, weak acid taste to Kimchi. But owing to lactic acid production by the homofermentative Lactobacillus plantarum, Kimchi finally reaches its acidified state. So, Leu. Mesenteroides was isolated from Kimchi and identified and was improved by mutation for carbon dioxide production at low pH, and for the high total acceptability. We tested with a wild-type strain K-1 and its improved mutant strain M-10 of Leu. Mesenteroides. The wild-type strain K-1 could grow in pH 4.2 at 30℃ or 20℃, and in pH 5.0 at 10℃. But the mutant strain M-10 could grow in pH 3.3 at 10℃. In the respect of total acceptability, mutant strain M-10 inoculated Kimchi was ever better than any others. Mutant M-10 inoculated Kimchi prolonged the optimum ripening period of Kimchi up to two times as compared with the control group.

흰쥐 대뇌피질에서 A₁ 아데노신 수용체의 탈감작

박경선(Kyung Sun Park),양완숙(Wan Suk Yang),김경환(Kyung Hwan Kim) 대한약리학회 1996 대한약리학잡지 Vol.32 No.2

Following the subcutaneous administration of R(-)N⁶-(2-phenylisopropyl)adenosine(600 nmol/kg/hr) to rats for 1 week using tAlzet^?? mini-osmotic pumps, A₁ adenosine receptor functions were determined using [³H]DPCPX binding, [³⁵S]GTP_γS binding, and adenylyl cyclase assays. A₁ adenosine receptor binding and the inhibition of adenylyl cyclase activity by PIA was not altered in cerebrocortical membranes prepared from PIA-treated rats. However, there was a significant decrease in the A₁ adenosine receptor-mediated stimulation of [³⁵S]GTP_γS binding to cerebrocortical membranes prepared from PIA-treated rats(22.0% decrease in basal activity; 19.7% decrease in maximal activity). These results suggest that the desensitization of A₁ adenosine receptors following chronic administration involves agonist-induced uncoupling of the receptors from G proteins rather than alteration of A₁ adenosine receptor molecules. It is also suggested that the determination of stimulation of [³⁵S]GTP_γS binding to G proteins is a suitable tool in studying the receptor regulation including desensitization

흰쥐의 뇌의A₁ 아데노신 수용체에 작용하는 역효현제에 관한 연구

박경선(Kyung Sun Park),양완숙(Wan Suk Yang),김경환(Kyung Hwan Kim) 대한약리학회 1996 대한약리학잡지 Vol.32 No.1

전통적인 수용체 이론에 따르면 상경적 길항제는 효현제와 수용체의 같은 부위에 작용하지만, 효능(efficacy)이 없기 때문에 생물학적 반응을 일으키지는 않는다. 그러나 최근에 발표되는 자료들에 따르면 모든 길항체의 효능(efficacy)이 0가 아니라 음수도 될 수가 있다고 생각된다. 이러한 음수의 효능을 갖는 약물을 역효현제라 부른다. 본 연구에서는 쥐의 cerebral cortex에서 얻은 membranes을 사용하여, A₁ 아데노신 수용체에 작용하는 역효현제를 인구하였다. 8개의 길항제로 알려진 약물들이 G단백에 대한 [³⁵S]GTP_γS 결합을 감소시키는 정도를 측정함으로써 역효현제의 특성을 검색하였다. 효현제에 의한 [³⁵S]GTP_γS 결합의 증가는 이틀 길항제틀에 의해 완전히 억제되었지만, 검색한 8개의 길항제는 두 군으로 구분되었다. DPCPX를 포함한 7개 길항제는 효현제 부재시의 basal [³⁵S]GTP_γS binding을 통계적으로 의의있게 감소시켜 역효현제의 특성을 나타내는 반면, CCS-15943은 basal [³⁵S]GTP_γS binding에 아무런 영향을 주지 않았다. NEM을 membranes에 처치하면 PIA에 의한 [³⁵S]GTP_γS binding이나 basal binding 둘다 감소하는데 이는 [³⁵S]GTP_γS binding의 상당부분이 G단백의 activated state를 나타내는 것을 알 수 있다. 또한 [³H]DPCPX를 이용한 competitive binding assay에서 0.1 mM GTP는 효현제인 PIA의 apparent affinity를 감소시켰으며, DPCPX의 apparent affinity는 증가시키고, CGS-15943에는 아무런 영향을 미치지 않았다. 이것은 상기의 [³⁵S]GTP_γS binding의 결과를 뒤받침해 주는 결과라고 생각된다. According to the traditional receptor model, competitive antagonists share with agonists the ability to bind to a common site on receptors, but they are different from agonist in that they cannot trigger the biological response-i.e., they lack intrinsic efficacy. Recent findings extend the model by indicating that not all antagonists display an intrinsic efficacy of zero but that some display inverse agonism . In the present study we studied the inverse agonism at A₁ adenosine receptors in membranes prepared from rat cerebral cortex. Eight commercially available A₁ adenosine receptor antagonists (CGS-15943, ADPX, CPT, DPCPX, DPX, N-0840, PACPX and 8-PT) were screened for inverse agonism by measuring the extent of [³⁵S]guanosine-5 -(γ-thio) triphosphate ([³⁵S]GTP_γS) binding to G proteins. The agonist-induced stimulation of [³⁵S]GTP_γS bindings was completely blocked in the presence of A₁ adenosine receptor antagonists. Under optimal conditions, two types of antagonists could be distinguished. Seven antagonists including DPCPX decreased the basal [³⁵S]GTP_γS binding in the absence of agonist, displaying inverse agonist activity. One (CGS-15943) had no effect on the basal bindings. N-ethylmaleimide treatment reduced the basal bindings as well as agonist-mediated stimulation of [³⁵S]GTP_γS bindings, indicating that a substantial amount of this binding reflects an activated state of the C proteins. In good agreement with these findings, 0.1 mM GTP decreased the apparent affinity of the receptors for the agonist PIA, increased that for DPCPX, and had no effect on that for CGS-15943.