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Prenylamine Lactate가 세포내 Organelles에서의 Ca++ -activated ATPase에 미치는 영향

Other Titles
 Effects of prenylamine lactate on the Ca++ -activated ATPase in subcellular organelles 
Issue Date
1975
Description
의학과/박사
Abstract
[한글] 각종세포내의 Ca**++의 농도는 이들 세포밖의 그것에 비하여 아주 적음에도 불구하고, Ca**++이 외부로 이동하는 현상은 에너지와 연관된 능동적인 이동이라는 기전이 과거 10 여년간 여러 학자들에 의해 밝혀졌고, 이때 Ca**++ -activated ATPase는 각종 생체막에서 Ca**++의 능동적인 이동 또는 Ca**++ uptake에도 중요한 매개체의 역할을 한다고 알려져 있다 (Hasselbach and Makinose, 1961; Vashington and Murphy, 1962; Schatzmann and V incenzi, 1969: Lee and Shin, 1969: Cha et al., 1971). 한편 여러가지 물질들이 Ca**++ 이동에 미치는 영향을 관찰하고 그 기전을 규명하려는 보고들이 많이 있다(Sanborn and Langer, 1970; Moore, 1971; Watson et al., 1971; Kohl hardt et al., 1972: Ong and Bailey, 1973: 박 및 강, 1973: Layton and Azzi, 1974: 이 등, 1975). 임상에서 관상동맥 확장제로 쓰이는 prenylamine lactate(Segontin**(R))는 Kloot(1973 )에 의하여 처음으로 가재근육에서 Ca**++ spikes를 억제시킨다고 보고 되었으며, 그 후 이 및 강(1974)은 적혈구막에서 Ca**++ -activated ATPase 활성도를 억제하므로써 Ca**++ 이동을 억제시킨다고 하였으며, Ca**++과 prenylamine lactate가 서로 상경적 억제작용( competitive inhibition)을 하기 때문이라고 하였다. 또한 강 및 이 (1975)는 이것이 토 끼 심근 세포막에서 Ca**++ influx를 억제하므로써 Bowditch 및 Woodworth staircase 현 상을 억제시킨다고 하였다. 따라서 본 실험의 목적은 적혈구막이나 다른 세포막에서 Ca**++ 이동을 억제시키는 pre nylamine lactate가 sarcoplasmic reticulum, mitochondria 및 actomyosin등과 같은 세포 내 몇몇 organelle에서의 Ca**++ -activated ATPase에 미치는 영향을 관찰하여 생체막에 서의 C**++ 이동기전의 일부를 규명하고져 했다. 실험방법으로는 흰쥐의 골격근에서 Fiehn 및 Peter(1971) 방법으로 분리한 sarcoplasmi c reticulum과, Levy 및 Fleisher(1965) 방법으로 분리한 actomyosin, 그리고 Chance 및 Williams(1955) 방법으로 흰쥐의 간에서 분리한 mitochondria에서, prenylamine lactate 가 Ca**++-activated ATPase 활성도에 미치는 영향을 Cha등(1971)의 방법으로 측정하였다 . 또한 Fiehn 및 Peter(1971) 방법으로 sarcoplasmic reticulum과 mitochondria에서 pren ylamine lactate가 Ca**45 uptake rate에 미치는 영향을 관찰하여 다음과 같은 결과를 얻 었다. 1. Prenylamine lactate는 흰쥐의 골격근에서 분리한 sarcoplasmic reticulum과 actomy osin, 및 흰쥐의 간에서 분리한 mitochondria에서의 Ca**++-activated ATPase를 활성도를 의의있게 억제하였으며, 이런 현상은 이 약물의 농도가 증가함에 따라 더욱 현저하었다. 2. Prenylamine lactate는 sarcoplasmic reticulum과 mitochondria에 의한 Ca**45 upta ke rate를 억제하였으며 이는 약물의 농도가 증가함에 따라 더욱 현저하였다. 이상의 성적으로 미루어 보아 prenylamine lactate는 세포막 뿐만 아니라 세포 각 orga nelle에서의 Ca**++-activated ATPase 활성도를 억제하므로써 Ca**++ 이동을 억제하는 것 으로 생각된다.
[영문] The energy-linked transports of Ca**++ in phosphorylating mitochondria and in the sarcoplasmic reticulum have been well established during the past decades (Hasselbach and Makinose, 1961 ; Ebashi and Lipmann, 1962: Brierley et al., 1964: Engstrom and De Luca, 1964: Hasselbach, 1964; Chance, 1965: Lee et at., 1966). Since free Ca**++ concentration gradient between extraand intra-cellular fluid is extremely large in tissues such as muscle and nerve, the existence of a similar Ca**++ pump mechanism in the cell membrane which is responsible for Ca**++ extrusion from these cells against an electro-chemical gradient has been suggested (Reuter and Seitz, 1968; Baker et al., 1969). It has been demonstrated that Ca**++ -activated ATPase is intimately linked to active transport of Ca**++ in red cells (Schatzmann and Vincenzi, 1969; Lee and Shin, 1969; Cha et al., 1971). The effects of several drugs identified as "Ca**++ -antagonists" on the Ca**++ transport systems have been reported (Sanborn and Langer, 1970; Moore, 1971; Watson et al., 1971; Koklhardt et al., 1972; Ong and Bailey, 1973; Park and Kang, 1973; Layton and Azzi, 1974; Lee et al., 1975). Prenylamine lactate (Segontin**(R)), which has been clinically used as a coronary vasodilator, has been reported to block Ca**++ spikes in crayfish muscle (Kloot, 1973), and also inhibits both the Ca**++ transport across the human red blood cell membrane and the Ca**++ -activated ATPase activity of the membrane (Lee and Kang, 1974). Also prenylamine lactate preferentially blocked Bowditch staircase phenomena in the rabbit cardiac muscle (Kang and Lee, 1975). All the above results suggest that prenylamine lactate inhibits the Ca**++ transport across the plasma membrane, but no experimental study was carried out on the effects of the drug on subcellular organelles. In the present study an attempt was made to investigate the effects of prenylamine lactate on Ca**++ -activated ATPase in the sarcoplasmic reticulum, actomyosin, and mitochondria, and to elucidate some mechanism of Ca**++ transport across these subcellular organelles. Methods 1. Preparations of sarcoplasmic reticulum, actomyosin and mitochondria: Sarcoplasmic reticulum and actomyosin were isolated from the skeletal muscle of the white rats without regard to sex according to the methods described by Fiehn and Peter (1971) and Levy and Fleisher (1965), respectively. Mitochondria was isolated from the liver of the rat by the method of Chance and Williams (1955). 2. Effects of prenylamine lactate on Ca**++ -activated ATPase activity in sarcoplasmic reticulum, actomyosin and mitochondria were measured by the method of Cha et al. (1971). 3. Effects of prenylamine lactate on Ca**++ uptake rate in sarcoplasmic reticulum and mitochondria were measured by the method of Fiehn and Peter (1971). Results and Conclusions 1. Prenylamine lactate was found to inhibit significantly Ca**++ -activated ATPase in the sarcoplasmic reticulum and in the actomyosin of the rat skeletal muscle, and also in the mitochondria of the rat liver. The inhibitory effects were proportional to the concentration of the agent. 2. Prenylamine lactate also inhibited Ca**45 uptake rate both in the sarcoplasmic reticulum and in the mitochondria. The effects were also concentration-dependent. From the above findings it may be concluded that prenylamine lactate can inhibit Ca**++ transport as it blocks Ca**++ -activated ATPase in subcellular organelles.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/115388
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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