Abstract
The effects of morphine on the transmembrane potential and the short circuit current in the isolated frog skin were studied under different experimental conditions. The measurem ents of the transmembrane potential and the short circuit current were carried out according to Ussing and Zerahn's method. Experimental results were summerized as follows: 1) $5{\pm}10^{-3}$M of morphine markedly depressed the transmembrane potential and the short circuit current of the naive preparation. The peak of these inhibitory effects of morphine was observed about 1 hour after administration of the drug. 2) However $10^{-4}$M of naloxone did not affect these effects of morphine. 3) Decrease of $K^+$, increase of $K^+$ or $Ca^{2+}$ in the perfusate, markedly potentiated the inhibitory action of morphine on both transmembrane potential and short circuit current of the frog skin, and addition of $Mn^{2+}$ to the solution depressed the effect of morphine on the transmembrane potential, while the inhibitory effect of morphine on the short circuit current was diminished in the $Ca^{2+}$-free ringer solution, and increase of $Mg^{2+}$ concentration depressed those effect of morphine on both electrical parameters. 4) In the morphine treated preparations, transmembrane potential and short circuit current were decreased in the early phase of drug treatment ($1{\sim}2$ days), but gradually increased to the significantly high level from the control (48 days after treatment). In these preparations, the effects of morphine on both electrical parameters were also potentiated in the early phase, but markedly diminished in the late phase of treatment. From the above results, it is postulated that the pharmacological actions of morphine as well as development of the tolerance by morphine may be partially related to the changes of ion fluxes and/or permeabilities of skin by the drug.
정상 또는 morphine을 처리한 개구리(Rana nigromaculate)의 피부에서 Ussing 등의 방법에 의하여 막전위와 단락전류에 미치는 morphine의 작용과 morphine 작용에 미치는 전해질의 영향을 관찰하여 다음과 같은 성적을 얻었다. 1) Morphine $5{\pm}10^{-3}$은 개구리 피부의 막전위와 단락전류를 현저히 감소시켰으며 약물투여후 60분후에 최고의 효과를 나타냈다. 2) Naloxone $10^{-4}$은 morphine의 막전위 및 단란전류 억제작용을 차단치 못하였다. 3) 영양액내 $Na^+$ 농도감소, $K^+$ 농도증가 및 $Ca^{2+}$농도증가는 morphine의 막전위 및 단란전류 억제작용ㅇ르 현저히 강화하였으며, $Mn^{2+}$첨가는 morphine의 막전위 억제효과만을 강화시켰다. 한편 $Ca^{2+}$ 농도의 감소로써 morphine의 단락전류억제 효과는 현저히 약화되었으며 $Ma^{2+}$농도 감소로써 morphine의 단락전류 억제효과로 더불어 막전위 억제효과도 감약되었다. 4) Morphine 처리 표본에서 막전위와 단락전류는 morphine 처리 초기에 일시적인 감소를 일으킨 후 증가하여 morphine 처리 $4{\sim}8$일에는 대조군에 비하여 현저히 상승하였다. 또한 morphine의 막전위 및 단락전류 억제효과에 있어서도 morphine처리 $1{\sim}2$일에는 morphine의 억제효과가 강화되나 morphine의 처리 4 또는 8일에는 현저히 약화되었다. 이상의 실험성적으로 morphine의 약물내성을 포함한 그 약리적작용이 생체막에서의 전해질수송 또는 전해질 투과성에 영향을 미쳐 초래될 수 있음을 시사하는 것으로 추측하였다.
(Department of Pharmacology, Jeonbuk Natl. University Medical School)
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