Uptake and Storage Mechanism of 5-Hydro-Xytryptamine in Rabbit Brain Stem and Effect of Reserpine

Abstract

In a previous paper (1) to clarify the physiological significance of endogenous 5-hy droxytryptamine (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 P2-fraction which consisted largely of mitochondria and nerve-ending particles (NEPs). After density-gradient centrifuga tion 5-HT was found to be comparatively highly concentrated in NEPs-fraction (P2B fraction). On the other hand suspension of P2-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 P2D and P,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 distrib uted among several fractions.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 fol lowing consecutive steps: 1) release of transmitter by synaptic impulses. 2) combination of transmitter with postsynaptic receptor. 3) generation of impulses by postsynaptic po tential. It appears that the study into the formation, uptake, storage, release and in activation of 5-HT is necessary for full and accurate understanding of mechanism of chemi cal transmission, especially when there is no direct evidence for that 5-HT is synaptic trans mitter in central nervous system. Segawa and Kuruma (4), Segawa et al. (5) in this la boratory have already shown that NEPs or sv of brain, when incubated in a medium con taining 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 under Reprints requests and enquiries should be sent to Tomio Segawa,