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학술저널

Rat적출심방 운동성에 대한 Prostaglandin F<sub>2</sub> alpha와 Ouabain작용의 비교

Comparative Effects of Prostaglandin F<sub>2</sub> alpha and Ouabain on the Isolated Rat Atria

PGE<sub>2α</sub>의 rat적출심방에 대한 작용을 ouabain의 작용과 비교하여 다음과 같은 결과를 얻었다. PGE<sub>2α</sub>의 양성변력성작용은 ouabain의 작용에 비해 potency가 강하고 efficacy는 낮았다. Ouabain은 PGE<sub>2α</sub>의 양성변시성작용과 유사한 양성변시성 경향을 나타내었는데 이 점에 대해 추후의 탐구가 요구된다. PGE<sub>2α</sub>(3 × 10<sup>-8</sup>M)의 작용은 저칼슘농도(1.4mM)에서 ouabain(3 × 10<sup>-3</sup>M)보다 현저히 (≤0.05 ~ p≤0.00)강하게 나타났고, medium내에 첨가되는 Ca<sup>++</sup>에 대하여도 보다 예민하게 반응하였다. 저칼륨 medium(2.8mM) 또는 medium내 K<sup>+</sup>첨가는 PGE<sub>2α</sub>보다 ouabain의 작용에 더 큰 영향을 미쳤다. PGE<sub>2α</sub>와 ouabain의 작용에 미치는 lidocaine (1 × 10<sup>-5</sup>M이상의 고농도)의 영향은 매우 흡사하여 별다른 차이점을 볼 수 없었다. Propranolol (3 × 10<sup>-6</sup>M)로써 전처치하여 아드레나린성 β수용체를 봉쇄한 적출심방에서 PGE<sub>2α</sub> 양성변력성 및 양성변시성 작용은 방해를 받지 않았다. 이상의 결과로 보아 PGE<sub>2α</sub>는 ouabain의 Na<sup>+</sup>, K<sup>+</sup>-ATPase 억제기전파는 달리 PGE<sub>2α</sub> 고유의 막수용체에 작용하여 Ca<sup>++</sup>의 세포내 유입을 촉진시키는 기전으로 작용하는 것으로 추측되며, 그 수용체의 등정(identification)은 추후의 연구과제로 남는다.

Comparative effects of PGE<sub>2α</sub> and ouabain on the isolated rat(Sprague-Dowley) atria were studied. The isolated rat atria were prepared for isometric myography in the isolated organ bath containing Feigen s solution perfused with 95% O<Sub>2</sub> and 5% CO<sub>2</sub>, and the pH of the medium was maintained at 7.4. The cumulative concentration-response relationship revealed the positive inotropic effects of both drugs with the higher potency of PGE<sub>2α</sub> and the higher efficacy of ouabain. PGE<sub>2α</sub> showed a positive chronotropic effect, but ouabain showed a tendency of increasing the contraction rate. In low-Ca(1.4 mM) medium, the positive inotropic and chronotropic effect of PGE<sub>2α</sub>(by 3 × 10<sup>-8</sup>M) were preponderant (p<0.05 ~ p<0.005) over those of ouabain(by 3 × 10<sup>-3</sup>M). Ca<sup>++</sup>-addition(cumulative, to 2.8, 4.2, 5.6, and 7.0 mM) into the medium evoked the more sensitive response in the PGE<sub>2α</sub> group than in the ouabain group. In low-K(2.8 mM) medium, the PGE<sub>2α</sub>(3 × 10<sup>-8</sup>M) group and the ouabain(3 × 10<sup>-3</sup>M) group showed similar tensions(DT and RT) and contraction rates. And both group showed significantly(p<0.05p<0.01) higher tensions and contraction rates than those of the control group. By the cumulative addition of the K<sup>+</sup>(to 4.2, 5.6, 7.0 and 8.4 mM), only the DT of the PGE<sub>2α</sub> group was sustained at signifcantly(p<0.05 ~ p<0.01) higher level than the DT of the control group. The K<sup>+</sup>-addition inhibited the positive inotropic effect of ouabain significantly (p<0.05). The cumulative addition of lidocaine in high concentrations (1 × 10<sup>-5</sup> to 1 × 10<sup>-3</sup>M) evoked no significant influence on the intropic activities of PGE<sub>2α</sub> and ouabain, but significant β-blockade with propranolol could not inhibit the positive intropic and chronotropic effect of PGE<sub>2α</sub>. In conclusion, it is presumed that PGE<sub>2α</sub> may have some more active mechanism of accelerating the influ× of Ca<sup>++</sup> across the cell membrane of the isolated rat atria as compared with ouabain, and the action site may be located at the cell membrane. As a supposition which needs further investigations, it is presumed that PGE<sub>2α</sub> may have its specific membrane receptors on the atrial muscle or sinus node cells.

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