초록
실험적으로 명암에 적응시킨 백서의 뇌내 specific opiate binding과 ${\beta}-endorphin$ 함량 일중변동에 미치는 지속적인 암적응, phenobarbital 장기처리의 영향을 관찰하고 opiate recptor binding과 ${\beta}-endorphin$ 함량 양자간의 관계를 추구하여 다음과 같은 성적을 얻었다. 1. L : D, 12 : 12 주기에 적응시킨 대조군에서 maximum $(^3H)$-morphine binding과 뇌내 ${\beta}-endorphin$ 함량은 각각 22시 및 06시에 최고에 달하는 매우 특이한 일중변동을 보였고 24시간 평균 $(^3H)$-morphine binding 및 뇌내 ${\beta}-endorphin$ 함량은 각각 0.45+0.03 pmol/mg protein과 46.7+3.6 fmol/mg protein이었다. 2. D : D, 12 : 12 주기에 적응시킨 표본에서 maximum $(^3H)$-morphine binding과 뇌내 ${\beta}-endorphin$ 함량은 대조군에서와는 달리 02시 및 14시에 최고에 달하는 유의한 일증변동을 보였고, 24시간 평균 maximum $(^3H)$-morphine binding치는 0.36+0.03 pmol/mg protein으로 대조군에 비하여 유의하게 감소를 하였으며, 24시간 정균 뇌내 ${\beta}-endorphin$치는 35.9+3.1 fmol/mg protein으로 대조군에 비하여 유의한 감소를 보였다. 3. Phenobarbital처리 표본에서 maximum $(^3H)$-morphine binding과 뇌내 ${\beta}-endorphin$ 함량은 각각 02시 및 14시에 최고 그리고 14시 및 02시에 최저에 달하는 대조군과는 다른 일중변동을 보였고, 24시간 평균 maximum $(^3H)$-morphine binding치는 0.33+0.03 pmol/mg protein으로 대조군에 비하여 현저한 감소를 보였다. 4. 전 실험군에서 opiate receptor binding의 Kd치는 변동하지 않았다. 5. 전 실험군에서 maximum $(^3H)$-morphine binding은 ${\beta}-endorphin$ 함량과 유의한 역상관관계가 있었다. 이상의 실험성적은 phenobarbital이 뇌내 ${\beta}-endorphin$ 함량과 opiate수용체의 숫적변동을 일으켜 morphine의 약리적 작용을 변동시킬 수 있으며, 이와 더불어 opiate 수용체와 ${\beta}-endorphin$ 함량 일중변동을 변화시킬 수 있음을 보여준다.
To investigate the influence of phenobarbital sodium on the action of morphine and on the diurnal rhythms of both opiate receptor binding and ${\beta}-endorphin$ contents, the amount of specifically bound $(^3H)$-morphine and immunoreactive ${\beta}-endorphin$ were measured in the midbrain of phenobarbital-treated rats at 4h intervals in a day. Rats were housed and adapted to a controlled cycle of either 12 h light-12 h dark or 24 h constant dark. After 3 weeks of adaptation, 0.5 ml of physiological saline or phenobarbital sodium (20mg/kg/day, i.p.) were administered twice a day for 2 weeks. Highly significant diurnal rhythms of opiate receptor binding and ${\beta}-endorphin$ were present in rat midbrain. In control group, the peak of maximum $(^3H)$-morphine binding was observed at 22:00 h, whereas the peak of ${\beta}-endorphin$ content was found at 06:00 h. Even in the absence of time cues these diurnal rhythms persisted, but they were highly modified with respect to the wave form as well as differences in the timing of peak and nadir. In the phenobarbital-treated group, these diurnal rhythms were also modified in shape, phase and amplitude, as well as in timing of peak and nadir. In this group, 24 h mean of opiate receptor binding was significantly decreased, while the 24 h mean level of ${\beta}-endorphin$ content was highly increased. However, Kd values in all experimental groups did not change. This indicates that differences in binding were not due to changes in the affinity, but in the number of binding sites. Statistical analysis of regression line indicates that changes of receptor binding were closely correlated with the changes of ${\beta}-endorphin$ content. These results suggest that phenobarbital may influence the action of morphine by changing the number of opiate receptors and that the modification of diurnal rhythm of opiate receptor by the agent is possibly due to changes of ${\beta}-endorphin$ content.