The influences of drugs on the uptake of 5-hydroxytryptamine by nerve-ending particles of rabbit brain stem

Segawa, Tomio; Kuruma, Isami

doi:10.1111/j.2042-7158.1968.tb09750.x

Cited by 42 publications

(8 citation statements)

References 12 publications

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“…The hip pocampus and frontal cortex were dissected out according to the method of Glowinski and Iversen (7). Crude synaptic membrane frac tions and crude mitochondrial P2 fractions were prepared according to the method described previously (1,8). The P2 fractions were dispersed in 10 volumes (vol./wt.)…”

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confidence: 99%

Chronic effects of imipramine and lithium on postsynaptic 5-HT1A and 5-HT1B sites and on presynaptic 5-HT3 sites in rat brain.

Mizuta¹,

Segawa²

1988

Jpn.J.Pharmacol

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Abstract-The effects of chronic treatment with imipramine, a tricyclic antidepres sant, or lithium, an antimanic-depressive illness drug, on postsynaptic serotonin-1A (5-HT1A) and 5-HT1B sites and on presynaptic 5-HT3 sites in the frontal cortex and hippocampus from rat brains were studied. Chronic i.p. administration (21 days) of imipramine reduced the maximum number of binding sites (Bmax) for postsynaptic 5-HT1A as monitored by the radioligands 3H-5-HT or 3H-8-hydroxy-2-(di-npropylamino)tetralin (3H-8-OH-DPAT), but did not change the Bmax for postsynaptic 5-HT1B and presynaptic 5-HT3 in either the frontal cortex or the hippocampus. Chronic i.p. administration (21 days) of lithium reduced the Bmax for postsynaptic 5-HT1A sites in the hippocampus, but not in the frontal cortex. There was a specific difference between imipramine and lithium regarding the inhibitory effect on postsynaptic 5-HT1A sites in the frontal cortex.In addition, lithium decreased the affinity of presynaptic 5-HT3 sites in the hippocampus.These findings may be also consistent with the inhibitory effect of lithium on presynaptic autoreceptors, which results in an increase of 5-HT release.

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confidence: 99%

Chronic effects of imipramine and lithium on postsynaptic 5-HT1A and 5-HT1B sites and on presynaptic 5-HT3 sites in rat brain.

Mizuta¹,

Segawa²

1988

Jpn.J.Pharmacol

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“…Our previous results (4,5) in which NEPs and sv were found to be able to take up 5-HT from the medium do not per se mean that these structures are the storage sites for 5-HT. To observe how much proportion of 5-HT which was taken up by P2-fraction was associated with sv fraction the following experiments were performed.…”

Section: -Ht Uptake By Subcellular 11-actionsmentioning

confidence: 99%

“…The method of fractionation was based on that previously employed in this laboratory (4,5). The subcellular fractions were suspended in Krebs…”

Section: Methodsmentioning

confidence: 99%

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

1971

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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,

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“…The brain stem of about 2.5 g was dissected, homogenized with a Teflon pestle in an ice-cold 0.32 M sucrose which contained 5 x 10-s M pheniprazine and was made up to about 25 ml. The method of the fractionation of P,-fraction (debris) and P,-fraction (crude mitochondria) was the same as that described previously (5). The microsomal P,-fraction was separated by centrifuging supernatant from P,-fraction at 100,000 ,p-, for 30 minutes, leaving a final suner natant, S3-fraction containing the soluble constituents of cytoplasmic material.…”

Section: Methodsmentioning

confidence: 99%

“…The microsomal P,-fraction was separated by centrifuging supernatant from P,-fraction at 100,000 ,p-, for 30 minutes, leaving a final suner natant, S3-fraction containing the soluble constituents of cytoplasmic material. Nerve ending particulate P,B-fraction was obtained from P2-fraction by means of a discontinuous density gradient centrifugation as described by Segawa and Kuruma (5). Synaptic vesi cular P,V-fraction and soluble supernatant P,VS-fraction were obtained by osmotic shock and centrifugation of P,-fraction with a procedure described previously (6).…”

Section: Methodsmentioning

confidence: 99%

Effects of Reserpine and Desipramine on the Uptake and Subcellular Distribution of 5-Hydroxytryptamine in Rabbit Brain Stem After Intravenous Administration of 5-Hydroxytryptophan

The influences of drugs on the uptake of 5-hydroxytryptamine by nerve-ending particles of rabbit brain stem

Cited by 42 publications

References 12 publications

Chronic effects of imipramine and lithium on postsynaptic 5-HT1A and 5-HT1B sites and on presynaptic 5-HT3 sites in rat brain.

Chronic effects of imipramine and lithium on postsynaptic 5-HT1A and 5-HT1B sites and on presynaptic 5-HT3 sites in rat brain.

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

Effects of Reserpine and Desipramine on the Uptake and Subcellular Distribution of 5-Hydroxytryptamine in Rabbit Brain Stem After Intravenous Administration of 5-Hydroxytryptophan

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