학술논문
白鼠腦의 Subcellular 分劃에 對한 D-LSD 및 Serotonin 誘導體들의 통합에 관한 실질적 연구
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- 영문명
- BINDING OF D-LSD AND SEROTONIN DERIVATIVES TO THE SUBCELLVLLAR FRACTIONS OF THE RAT BRAIN
- 발행기관
- 대한신경정신의학회
- 저자명
- 金振國 李定均
- 간행물 정보
- 『신경정신의학』제19권 제4호, 331~339쪽, 전체 9쪽
- 주제분류
- 의약학 > 정신과학
- 파일형태
- 발행일자
- 1980.11.30
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국문 초록
영문 초록
Although the existence of serotonergic neurons in the brain has been confirmed by both electrophysiologically
and the distribution of a ㅣarge amount of serotonin (5-hydroxy tryptamine) in the brain , the ultimate neurochemical approach
lies in the identification ofthe serotonin rebeptor to which serotonin, its agonists and antagonists
bind in a very specific manner. The criteria for the specific binding of serotonin derivatives to
the receptor are : (1) the binding must be saturable ; (2) stereospecific ; (3) of high-affinity
and ; (4) the displacement of the serotonin binding by other serotonergic ligands should reflect
the physiological and pharmacological Potencies of these drugs.
Serveral laboratories including ours have identified the serotonin receptor by use of tritiated
lysergic acid diethylamide (L SD ). The general procedure consists of (1) incubation of H3-LSD
with subellular fragments of different degree of purities, (2) filtra tio n of the incubates on a
glase filte r G-F/B, and counting of the radioactivity of the bound LSD in a scintillation
counter. The displacement study, of the LSD binding by various ligands involves incubation
of LSD and subcellular fragments with adding the ligands of different concentration.
The results show that LSD binds to various subcellular fractions with a dissociation constant
(Kd) of 11.0xl0~9M. The binding is saturable and stereospecific in the sense that 1-LSD, a physiologically inactive optical isomer of d-LSD, does not interfere the specific binding. The max
imum specific binding is observed with a disrupted P4 microsomal membrane fraction. Binding
study using different fractions of the rat brain show that the dissociation constant does not vary
from fraction to fraction. However, there is a great variation in the maximum specific binding.
Maximum specific binding of the crude homogenate is only 0.27 picom이/ mg protein, whereas
in the case of the vigorously dsurupted P4 membrane fraction the m aximum sipecific binding
is 2.3 picomole/mg protein.
The specific binding can be displaced by the various tryptam ine derivatives. The DC50, the
concentration at 50% displacement, of try ptamine derivatives has the following order : 5-0H =
5-MeO> 4-OH> 5-CH3> F > 5,6-(OH)2> 5-F>7-0 H4-NH2〉7-OH>6-ᄋH〉7-MeO. This order is in
agreement w ith the potencies of these drugs in contracting the smooth muscle investigated by
John Vane.
Amphetamine and mescaline derivatives are usually 100 times less potent than the tryptamine
derivatives. Likewise, the binding of d-LSD does not seem to be associated with the hallucinogenic
activity of this drug, because 2-Bromo-LSD, a non-hallucinogen, is as potentas d-LSD in the
displacement of the d-LSD binding. Another serotonin antagonist cyproheptadine, but a nonhallucinogen,
shows asimilar displacement. It appears that the serotonin receptor, so identified,
is not a receptor which is responsible for the hallucinogenic activity.
The membrane destabilizing factors such as hypoosmotic shock, treatment with phospholipase
Cor EGTA, increase the m axim um LSD binding.
Treatment with trypsin or protease decreases greatly the specific binding demonstrating that
the serotonin receptor is a protein imbedded in a phospholipid matrix of the synaptic membranes
목차
緖 論
實驗方法 및 實驗材料
實驗 結果
考 察
結 論
REFERENCES
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