UPTAKE AND STORAGE MECHANISM OF 5-HYDRO-XYTRYPTAMINE IN RABBIT BRAIN STEM AND EFFECT OF RESERPINE
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概要
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In a previous paper (1) to clarify the physiological significance of endogenous 5-hydroxytryptamine (5-HT) the subcellular distribution of 5-HT in rabbit brain stem has been studied and the electron microscopical structures of the fractions which contain 5-HT have been examined. 5-HT was principally found in P<SUB>2</SUB>-fraction which consisted largely of mitochondria and nerve-ending particles (NEPs). After density-gradient centrifugation 5-HT was found to be comparatively highly concentrated in NEPs-fraction (P<SUB>2</SUB>B-fraction). On the other hand suspension of P<SUB>2</SUB>-fraction in hypo-osmotic medium and subsequent differential centrifugation resulted in high concentration of 5-HT in synaptic vesicles (sv) fraction although considerable amount of 5-HT was also found in P<SUB>2</SUB>D- and P<SUB>2</SUB>S-fraction. In general 5-HT in brain stem was not so highly concentrated in specific fraction as with the distribution of acetylcholine (ACh) (2, 3) but rather diffusibly distributed among several fractions.<BR> In this paper the role of 5-HT in synaptic transmission, especially in central nervous system was investigated mainly through the experiments on 5-HT uptake by subcellular fraction of rabbit brain stem. The chemical transmission at synapses consists of the following consecutive steps: <I>1</I>) release of transmitter by synaptic impulses. <I>2</I>) combination of transmitter with postsynaptic receptor. <I>3</I>) generation of impulses by postsynaptic potential. It appears that the study into the formation, uptake, storage, release and inactivation of 5-HT is necessary for full and accurate understanding of mechanism of chemical transmission, especially when there is no direct evidence for that 5-HT is synaptic transmitter in central nervous system. Segawa and Kuruma (4), Segawa et al. (5) in this laboratory have already shown that NEPs or sv of brain, when incubated in a medium containing 5-HT, could take up 5-HT from the medium and some drugs could inhibit the uptake of 5-HT. However we have as yet very little information as to whether NEPs or sv are specific uptake and storage site for 5-HT in situ. Also the mechanisms with which amine can be taken up by synapses and drug inhibits the uptake are poorly understood. The following is a systematic study concerning the mechanism of 5-HT uptake and drug effect.
- 公益社団法人 日本薬理学会の論文
著者
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Segawa Tomio
Department Of Pharmacology Institute Of Pharmaceutical Sciences Hiroshima University School Of Medic
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Takagi Hiroshi
Department Of Bioscience Faculty Of Bioscience Fukui Prefectural University
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Takatsuka Katsuya
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University
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