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1.
Effects of 5-hydroxytryptophan on serotonin in nerve endings 总被引:1,自引:1,他引:0
—Preparations of synaptosomes (P2) from the telencephalon and from the diencephalon plus optic lobes of the pigeon and from the telencephalon of the rat were used to study the effects of 5-hydroxytryptophan (5-HTP) on (a) the levels of serotonin (5-HT) in nerve endings and (b) the release of 5-HT from nerve endings. The levels of 5-HT were significantly higher (3.21 × 0.35 nmol/g original tissue weight) in the P2 fraction isolated from the telencephalon of pigeons given intramuscular injections of 50mg/kg of d ,l -5-HTP in comparison to control values (1.42 ± 0.07). A similar twofold increase was observed with the P2 fraction isolated from the diencephalon plus optic lobes. In addition, the levels of 5-HTP and 5-hydroxyindoleacetic acid also increased significantly in these P2 fractions isolated from pigeons given d ,l -5-HTP injections in comparison to values obtained for pigeons given saline injections. In vitro studies using preparations of synaptosomes (from both pigeon and rat) labelled with [3H]5-HT indicated that 0.10 mil l -5-HTP increased the release of [3H]5-HT twofold over control values. A concentration as low as 0.001 mm l -5-HTP was tested on the P2 fraction from the telencephalon of the pigeon and was found to significantly increase the release of [3H]5-HT over control values. This effect by l -5-HTP was blocked if a decarboxylase inhibitor was added to the medium. l -5-HTP at a concentration of 1.5 mm had no apparent effect on the release of [3H]norepinephrine or [3H]dopamine from synaptosomes prepared from the telencephalon of the rat or pigeon. The results are discussed in terms of the role of serotonin in producing certain types of behavioral depressions exhibited by pigeons and rats given injections of 5-HTP. 相似文献
2.
J. E. Smith J. N. Hingtgen W. J. McBride M. H. Aprison 《Journal of neurochemistry》1976,27(3):747-751
Abstract— Pigeons working on a multiple fixed ratio 50, fixed interval 10 schedule for food reinforcement were killed at 0, 50, 90, 150 and 240 min after an i.m. injection of 300mg/kg l -tryptophan. The levels of tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine, 5-hydroxyindole acetic acid, tyrosine, dopamine and norepinephrine were concurrently measured in crude nerve ending fractions (P2 ) isolated from the telencephalon, diencephalon plus mesencephalon and pons plus medulla-oblongata of each pigeon. Increases in 5-hydroxytryptamine levels in the nerve ending fraction from the telencephalon were correlated with the onset of the decreased response rates, whereas a return to baseline responding was correlated with a return to normal serotonin levels in this fraction. Changes in dopamine or norepinephrine were not related to the onset of or recovery from the decreased response rate. One group of pigeons were found which did not display any behavioral disruption even though each had received an injection of l -tryptophan; the content of 5-hydroxytryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the nerve ending fraction isolated from the telencephalon of these birds did not differ from control values. 相似文献
3.
UPTAKE OF ACETYLCHOLINE AND CHOLINE INTO RAT BRAIN CORTICAL SLICES AND SYNAPTOSOMES AS RELATED TO 32 Pi , INCORPORATION INTO THEIR PHOSPHOLIPIDS 总被引:2,自引:0,他引:2
—The role of ACh-stimulated 32Pi incorporation into the phospholipids of rat cerebral cortex slices and isolated nerve endings (synaptosomes) has been studied. ACh stimulation is not connected with any carrier-mediated uptake of ACh. Such uptake may occur in slices in the presence of the anticholinesterase Sarin but barely in the presence of eserine. Regardless of the nature of the anticholinesterase used, rat cerebral cortex synaptosomes that respire and show high and low affinity choline uptake do not accumulate ACh against a concentration gradient. At exogenous ACh concentrations of 10–5m and above, some ACh enters the synaptosomes by diffusion and significantly stimulates 32Pi incorporation into phosphatidic acid. It is discussed whether, in isolated nerve endings, an increase in cytoplasmic ACh concentration due to diffusion may induce vesicle turnover to keep a balance between ‘free’ and bound ACh or if a presynaptic ACh receptor is responsible for the observed changes in phosphatidic acid. The distribution of accumulated radioactivity derived from exogenous choline and ACh respectively between ACh, choline, phosphorylcholine and betaine has been studied in slices and isolated nerve endings. 相似文献
4.
The release of [3H]5-hydroxytryptamine ([3H]5-HT) byl-5-hydroxytryptophan (L-5-HTP),-methyl-m-tyramine (-MMTA), and elevated levels of K+ was studied using crude synaptosomal preparations (P2) isolated from the telencephalon of the rat and pigeon. Studies were conducted in vitro in the presence of either 2×10–5 M tranylcypromine, which inhibited the MAO activity of both the extrasynaptosomal mitochondria and the mitochondria contained within the nerve endings (intrasynaptosomal mitochondria), or 2×10–5 M nialamide, which inhibited the MAO activity of the extrasynaptosomal mitochondria under the experimental conditions used. In the P2 fraction isolated from the rat, either 55 mM K+, 0.10 mMl-5-HTP, or 0.03 mM-MMTA significantly increased the release of [3H]5-HT above control levels, regardless of which MAO inhibitor was present in the medium. In the presence of tranylcypromine, this increased release by 55 mM K+ or 0.10 mMl-5-HTP was partially suppressed if Ca2+ was omitted from the medium. In the presence of nialamide, the release by 55 mM K+ was completely prevented if Ca2+ was omitted; the release byl-5-HTP was only partially affected. The release of [3H]5-HT by-MMTA did not appear to be markedly affected by removal of Ca2+, regardless of which MAO inhibitor was present. Very similar data were obtained in the presence of nialamide using the P2 fraction isolated from the telencephalon of the pigeon, with the exception that 0.10 mMl-5-HTP caused an increase in the release of [3H]5-HIAA (which was not calcium-dependent) instead of [3H]5-HT. The data are discussed in 相似文献
5.
Microdetermination of norepinephrine, 3,4-dihydroxyphenylethylamine, and 5-hydroxyyptamine from single extracts of specific rat brain areas 总被引:1,自引:0,他引:1
The conditions reported by Toru and Aprison (4) for extracting ACh in specific brain areas were tested to determine whether 5-HT, NE, and dopamine were also extracted quantitatively. It was found that the extraction solution used in brain ACh determinations, 15% 1N formic acid plus 85% acetone (), was also excellent for extraction of NE, 5-HT, and dopamine from different brain areas. Experimental conditions are given for the microdetermination of all three biogenic amines in such a single extract of a specific rat brain area. The methods are based on previously published fluorometric methods; these have been scaled down or modified slightly to permit analyses of small aliquots. The concentration of 5-HT, NE, and dopamine in the telencephalon, diencephalon plus mesencephalon, pons plus medulla oblongata, and cerebellum of the rat are also reported using the described micromethods after extraction with 15% 1 N formic acid plus 85% acetone (). 相似文献
6.
In rat striatal synaptosomes incubated with [14C]tyrosine, the evolution of 14CO2, taken as a measure of dopamine synthesis, was inhibited by exogenous dopamine and by the dopaminergic receptor agonist ADTN. The inhibition was not counteracted by dopaminergic receptor antagonists (haloperidol, sulpiride, pimozide or domperidone). Instead, it was prevented by dopamine uptake blockers, suggesting that dopamine and ADTN (a substrate of the dopamine carrier) acted once inside the nerve endings and not through activation of autoreceptors on their external membrane. The dopamine uptake inhibitors nomifensine, benztropine and cocaine increased 14CO2 evolution from incubated striatal synaptosomes. Depolarization with KCl also increased dopamine synthesis and this action was potentiated when the reuptake of the released catecholamine was prevented by carrier blockers. The rate of dopamine synthesis was lowered when synaptosomal dopamine was raised upon incubation with monoamine oxidase inhibitors or with l-DOPA. The inhibition was counteracted by dopamine reuptake blockers. The data suggest that dopamine synthesis in striatal nerve endings is under the inhibitory control of the transmitter recaptured following release. 相似文献
7.
Topography of synaptosomal high affinity uptake systems. 总被引:2,自引:0,他引:2
We have tested the hypothesis that the glycoproteins in the cell membrane of axonal terminals are involved in high affinity uptake of neurotransmitters by studying the effects of lectin binding and trypsin treatment on this process in synaptosomes. Binding of two lectins, Concanavalin A and a lectin isolated from the lentil Lens culinaris, to synaptosomes does not change the uptake of six putative transmitters: L-glutamate, norepinephrine (NE), 5-hydroxytryptamine (5-HT), dopamine, choline (Ch), and γ-aminobutyrate (GABA). While trypsin digestion of surface proteins of synaptosomes has no effect on the uptake of NE, 5-HT, dopamine, Ch and GABA, it reduces the rate of uptake of L-glutamate. This reduction is not due to synaptosomal lysis or a profound conformational change of the synaptic plasma membrane since the maximal velocity of high affinity uptake is reduced drastically with little attendant change in Km. 相似文献
8.
Abstract— This investigation was designed to determine whether the amount of serotonin (5-HT) in cultured pineal glands can be altered by norepinephrine (NE). Treatment with l -NE (10?5-10?7m ) for 4-6 h caused a gradual decrease in the concentration of 5-HT to a value that was less than 30% of that in the untreated control gland. This effect was observed using chronically denervated pineal glands. d -Norepinephrine (10?6-10?7m ) and dopamine (10?4m ) were ineffective in lowering 5-HT. The effect of l -NE was completely blocked by a β-adrenergic receptor blocker, propranolol and was only slightly decreased by α-adrenergic receptor blockers. These observations indicate that l -NE acts post-synaptically via a highly specific β-adrenergic mechanism. The effect of l -norepinephrine was mimicked by theophylline and N6, 2′0-dibutyryl adenosine 3′,5′-monophosphate, an indication that adenosine 3′,5′-monophosphate is involved in the effect of l -NE on 5-HT. Treatment with cycloheximide, which by itself caused a decrease in pineal 5-HT, also blocked any further decrease caused by treatment with l -NE, an indication that protein synthesis is necessary for maintenance of baseline levels of serotonin and for the effect of l -NE to be observed. The total amount of l -[3H]NE and degradation products of L-[3H]NE in the gland after 6 h of treatment with l -[3H]NE was less than 3 pmol. This amount of l -NE and degradation products of l -NE could not account for the decrease of 100-200 pmol of 5-HT on the basis of a mole for mole replacement of 5-HT by l -NE. These findings are consistent with the hypothesis that non-neuronal pineal 5-HT is physiologically regulated by the release of l -NE from the sympathetic nerve network. 相似文献
9.
Intrasynaptosomal conversion of tyrosine to dopamine as an index of brain catecholamine biosynthetic capacity 总被引:5,自引:5,他引:0
—The potential for intrasynaptosomal conversion of tyrosine to dopamine was evaluated in the cell bodies (substantia nigra) and nerve terminals (caudate-putamen) of the nigral-striatal dopaminergic pathway. The conversion technique involves measurement of 14CO2 evolved from carboxyl-labelled tyrosine in the absence of both exogenous pteridine cofactor and DOPA decarboxylase. Evaluation of apparent Km values for tyrosine uptake and conversion and observed maximal velocities suggest that conversion is not limited by movement of substrate into the synaptosomes. The results, based on brain regional and subcellular distribution, are consistent with the localization of conversion in nerve endings and suggest a rapid and reliable measure for catecholamine biosynthetic capacity when structural integrity of the nerve ending is maintained. 相似文献
10.
The distributions of noradrenaline and dopamine in subcellular fractions of bovine superior cervical ganglia were measured fluorimetrically and were compared with that of acetylcholine. Results indicate that the crude synaptosomal pellet (2), which contained the bulk of the bound acetylcholine, was not seriously contaminated with catecholamines. The microsomal fraction showed the highest concentration of noradrenaline relative to protein content, while dopamine was richest in 2, possibly due to formation of synaptosomes from nerve endings of the dopaminergic interneurones which have been described in this tissue. 相似文献
11.
Prakash KR Tamiz AP Araldi GL Zhang M Johnson KM Kozikowski AP 《Bioorganic & medicinal chemistry letters》1999,9(23):3325-3328
A series of N-phenylalkyl-substituted tropane analogs of boat conformation was synthesized, and these tropanes were evaluated for their ability to inhibit high affinity uptake of dopamine (DA) and serotonin (5-HT) into striatal nerve endings (synaptosomes). Some of these compounds exhibit high affinity for the DA transporter with a 5-HT/DA transporter selectivity ratio of >50. 相似文献
12.
Chronic treatment with p-chlorophenylalanine methylester (PCPA) resulted in enhanced sensitivity to D,L-5-hydroxytryptophan (5-HTP) induced inhibition of response rates in rats working on a Variable Interval 1 min schedule of milk reinforcement. Marked depletions of 5-hydroxytryptamine (5-HT) were found in the cerebral cortex, hippocampus, striatum, diencephalon, mesencephalon, and pons-medulla oblongata. Much smaller dopamine depletions were seen in some areas, particularly the hippocampus and pons-medulla oblongata. Analysis of the binding of [3H]5-HT to crude membrane fractions from the cerebral cortex of PCPA-treated animals indicated a significant decrease in the apparent dissociation constant (KdAPP) for 5-HT, but no change in the maximum binding capacity. The increased behavioral sensitivity to 5–HTP does not seem to be due to increased conversion of 5-HTP to 5-HT, increased uptake of 5-HTP, or release of 5-HT by p-chlorophenylethylamine. However, the possibility that p-chlorophenylalanine or the metabolite p-chlorophenylacetic acid increased the binding of 5-HT, thus decreasing KdAPP, cannot be ruled out. Some parallels between a recently proposed model of human depression and the observations of the present investigation are discussed. 相似文献
13.
The effects of 5-HT and glutamate on dopamine synthesis and release by striatal synaptosomes were investigated and compared with the action of acetylcholine, which acts presynaptically on this system. 5-HT inhibited (28%) synthesis of [14C]dopamine from L-[U-14C]tyrosine, at 10-5M and above. This contrasts with the action of acetylcholine, which stimulated [14C]-dopamine synthesis by 24% at 10-4 M. Tissue levels of GABA were unaffected by either 5-HT or acetylcholine up to concentrations of 10-4 M. The inhibitory action of 5-HT (5 × 10?5 M and 2 × 10?4 M) on [19C]dopamine synthesis was completely abolished by methysergide (2 × 10?6 M). Higher concentrations of methysergide (10?4 M) or cyproheptadine (10?5 M) inhibited [14C]dopamine synthesis by 28% and 25%, respectively, when added alone to synaptosomes. However, only methysergide prevented the further inhibition of synthesis caused by 5-HT. At concentrations of 2 × 10?5 M and above, 5-HT stimulated [14C]dopamine release. This releasing action differed from that of acetylcholine, which occurred at lower concentrations (e.g., 10?6 M). Methysergide (up to 10?4 M) or cyproheptadine (2 × 10?4 M) did not reduce the 5-HT (5 × 10?5 M)-induced release of [14C]dopamine, but methysergide (10?4 M) showed a potentiation (49%) of this increased release. The stimulatory effects of 5-HT (2 × 10?5 M) and K+ (56 mM) on [14C]dopamine release were additive, indicating that two separate mechanisms were involved. However, when both agents were present the stimulatory effect of K+ (56 mM) on [14C]dopamine synthesis was not seen above the inhibitory effect of 5-HT. Glutamate (0.1-5 mM) did not affect [4C]dopamine release or its synthesis from L-[U-14C]tyrosine. It is concluded that 5-HT modulates the synthesis of dopamine in striatal nerve terminals through a presynaptic receptor mechanism, an action antagonised by methysergide. The releasing action of 5-HT apparently occurs through a separate mechanism which is also distinct from that involved in the response to K+ depolarisation. 相似文献
14.
Abstract— The activities of each enzyme associated with the pentose phosphate pathway as well as the non-enzymatic intermediates in this pathway were measured in synaptosomes isolated from rat cerebral cortex. The specific activities of transketolase (EC 2.2.1.1) and transaldolase (EC 2.2.1.2) were significantly lower in synaptosomes than cerebral cortex; however, the specific activities of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), ribosephosphate isomerase (EC 5.3.1.6) and ribulosephosphate epimerase (EC 5.1.3.1.) were comparable in homogenates of synaptosomal fractions and cerebral cortex. Concentrations of most intermediates of the pentose pathway were also similar in extracts of synaptosomes and brain homogenates. Six hours after treatment of rats with the nicotinamide analog, 6-aminonicotinamide (6-AN), 6-phosphogluconate levels in synaptosomes were increased 5-fold; however, glucose-6-phosphate levels remained unchanged. During a 30 min in uitro incubation 6-phosphogluconate levels increased approx 2-fold in synaptosomes obtained from 6-AN treated rats but did not change in synaptosomes from untreated rats. During the same period glucose-6-phosphate levels decreased in synaptosomes from both control and 6-AN treated rats. The conversion of both [1-14C]glucose and [6-14C]glucose to 14CO2 was depressed in synaptosomes from 6-AN treated rats; however, the ratio of the two isotopes converted to 14CO2 was essentially the same. It is concluded that the pentose phosphate pathway is active in nerve endings both in vivo and in vitro. 相似文献
15.
Effect of Bicuculline-Induced Status Epilepticus on Prostaglandins and Hydroxyeicosatetraenoic Acids in Rat Brain Subcellular Fractions 总被引:7,自引:5,他引:2
Abstract: Rat cerebrum, prelabeled in vivo by intraventric-ular injection of [1-14C]arachidonic acid, was used to assess cyclooxygenase and lipoxygenase reaction products in total homogenates, cytosol, synaptosomes, and microsomes. Effects of bicuculline-induced status epilepticus on arachi-donic acid metabolism in synaptosomes and microsomes were also measured. Lipoxygenase activity, resulting in the synthesis of hydroxyeicosatetraenoic acids (HETEs), and cyclooxygenase activity, resulting in the synthesis of prostaglandins (PGs), were measured by reverse-phase and normal-phase HPLC with flow scintillation detection. Endogenous lipoxygenase products in synaptosomes were identified by capillary gas chromatography-mass spectrometry. PGs and HETEs were detected in all subcellular fractions. The synaptosomal fraction showed the highest lipoxygenase activity, with 5-HETE, 12-HETE, and leukotriene B4 as the major products. Following bicuculline-induced status epilepticus, endogenous free arachidonic acid and other fatty acids accumulated in synaptosomes, but not in microsomes. Incorporation of [1-l4C]arachidonic acid into synaptosomal and microsomal phospholipids was decreased after bicuculline treatment. Bicuculline-induced status epilepticus resulted in increased synthesis of HETEs in synaptosomes. PG synthesis increased in the microsomal fraction. When [1-14C]arachidonic acid-labeled synaptosomes and microsomes were incubated for 1 h at 37°C the synthesis of eicosa-noids, particularly PGD2, was increased significantly in bi-cuculline-treated rats, as compared with untreated rats. Depolarization (45 mM K+) of synaptosomes induced a loss of [1-14C]arachidonic acid from phosphatidylinositol, and increased the synthesis of PGD2 and HETEs, an effect that was enhanced in bicuculline-treated rats. This study localizes changes in arachidonic acid metabolism and lipoxygenase activity resulting from bicuculline-induced status epilepticus in the brain subcellular fraction enriched in nerve endings. 相似文献
16.
Abstract— The effects of i.p. injections of SO mg/kg d,l-5-hydroxytryptophan (5-HTP) and saline alone on the in uitro release of endogenous serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were studied using preparations of axon terminals (P2 isolated from the telencephalon of rats. The level of 5-HT was 2-fold greater and the level of 5-HIAA was 5-fold greater in the P2 fraction isolated from rats given the d,l-5-HTP injection than from rats given saline injections. At 37°C the in vitro efflux of 5-HT and 5-HIAA from the P2 fractions of animals injected with 5-HTP 30min before killing was approx 3 times higher than the saline control group. The amount of 5-HT and 5-HIAA released at 37°C was 3–5 times higher than the amount released at 0°C for both the 5-HTP and saline injected rats. Increasing the concentration of potassium ions in the media to 55 mm significantly increased the release of 5-HT but not 5-HIAA in both groups of animals. The amount of 5-HT released by 55mm-K+ was about 2-fold higher from the P2 fraction isolated from rats given 5-HTP injections with respect to those given saline injections. The potassium stimulated release of 5-HT was calcium dependent. The data thus indicate that injection of 50 mg/kg d,l-5-HTP in rats can cause an increase in the level of 5-HT and 5-HIAA in a crude synaptosomal fraction and that as a result of this increase, there is a temperature dependent increased release of 5-HT and 5-HIAA under normal resting membrane conditions. There is also an increased release of 5-HT as a result of membrane depolarizing conditions induced by elevated potassium levels which is calcium dependent. 相似文献
17.
S. K. Mahata Asok Ghosh 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1991,161(5):532-536
Summary Glucagon (0.1 mg · 100 g body wt-1) increased norepinephrine (NE) content in adult pigeon (31%) and parakeet (58%), decreased NE content in the adrenal medulla of newly-hatched pigeon (36%), parakeet (52%), and crow (44%) 0.5 h after treatment. Epinephrine (E) content decreased to 26% and 59% of control values, respectively, in newly-hatched pigeon and parakeet 0.5 h after treatment. Glucagon produced hyperglycemia irrespective of age and species. The results indicate that aging modulates glucagon-induced changes of catecholamine (CA) content. In the innervated (I) adrenal gland of pigeon, glucagon caused a 31% increase of NE content 0.5 h after injection, a 46% decrease of NE content 12 h after injection, and a 192% increase of NE 24 h after injection. In the I gland of pigeons, glucagon also caused a 61% decrease of E content 4 h after injection, and brought about a 100% increase of E 24 h after injection. Glucagon-induced changes of CA content differ significantly between the I and denervated (D) glands. The results indicate that the splanchnic nerve regulates release and/or resynthesis of CA induced by glucagon.Abbreviations
ANOVA
analysis of variance
-
CA
catecholamine
-
D
denervated
-
E
epinephrine
-
I
innervated
-
MS
mean sum of squares
-
NE
norepinephrine
-
PNMT
phenylethanolamine-N-methyl transferase
-
SS
sum of squares
-
SV
source of variation
-
TH
tyrosine hydroxylase 相似文献
18.
Maria Ereciska David Pleasure David Nelson Itzhak Nissim Marc Yudkoff 《Journal of neurochemistry》1993,60(5):1696-1706
Abstract: The pathways of nitrogen transfer from 50 μM [15N]aspartate were studied in rat brain synaptosomes and cultured primary rat astrocytes by using gas chromatography-mass spectrometry technique. Aspartate was taken up rapidly by both preparations, but the rates of transport were faster in astrocytes than in synaptosomes. In synaptosomes, 15N was incorporated predominantly into glutamate, whereas in glial cells, glutamine and other 15N-amino acids were also produced. In both preparations, the initial rate of N transfer from aspartate to glutamate was within a factor of 2-3 of that in the opposite direction. The rates of transamination were greater in synaptosomes than in astrocytes. Omission of glucose increased the formation of [15N]-glutamate in synaptosomes, but not in astrocytes. Rotenone substantially decreased the rate of transamination. There was no detectable incorporation of 15N from labeled aspartate to 6-amino-15N-labeled adenine nucleotides during 60-min incubation of synaptosomes under a variety of conditions; however, such activity could be demonstrated in glial cells. The formation of 15N-labeled adenine nucleotides was marginally increased by the presence of 1 mM aminooxyacetate, but was unaffected by pretreatment with 1 mM 5-amino-4-imidazolecarboxamide ribose. It is concluded that (1) aspartate aminotransferase is near equilibrium in both synaptosomes and astrocytes under cellular conditions, but the rates of transamination are faster in the nerve endings; (2) in the absence of glucose, use of amino acids for the purpose of energy production increases in synaptosomes, but may not do so in glial cells because the latter possess larger glycogen stores; and (3) nerve endings have a very limited capacity for salvage of the adenine nucleotides via the purine nucleotide cycle. 相似文献
19.
W. J. McBride P. E. Penn T. P. Hyde J. D. Lane J. E. Smith 《Neurochemical research》1976,1(4):437-449
The effects ofD,L--chlorophenylalanine methyl ester (PCPA-methyl ester) and two of its metabolites, 2-(-chlorophenyl)-ethylamine (PCPEA) and -chlorophenylacetic acid (PCPAA), on the metabolism of serotonin (5-HT) fromD,L-5-hydroxytryptophan (5-HTP) ware studied in vitro and in vivo using the telencephalon and brainstem of the rat. For in vivo studies and some in vitro experiments, rats were injected with either 100 mg/kg PCPA-methyl ester or saline alone on days 1, 2, and 3, and were killed on day 15. When the in vivo metabolism of 5-HT was to be studied, the saline group and the PCPA group of animals were injected with 75 g/kg [3H]D,L-5-HTP 20 min before sacrificing. With respect to the values found for the saline-injected animals, the specific activity (S.A.; dpm/nmol) of 5-HIAA was significantly greater in the telencephanol and brainstem of the animals injected with PCPA-methyl ester. The S.A. of 5-HTP was the same in both groups; the S.A. of 5-HT was lower in the telencephalon of the PCPA group than in the saline group; in the brainstem, there was no difference. In both the saline- and PCPA-injected animals, the S.A. of 5-HIAA was greater than the S.A. of 5-HT. There was no difference between the saline- and PCPA-injected animals with regard to: (1)L-5-HTP decarboxylase activity; (2)L-5-HTP-induced release of [3H]5-HT in vitro from crude nerve ending fractions (P2); or (3) in vitro uptake of [3H]D,L-5-HTP and its conversion to [3H]5-HT using the P2 fraction. In vitro studies demonstrated that the PCPEA could directly cause a large increase in the release of [3H]5-HT from the P2 fraction, whereas PCPA and PCPAA had little or no apparent effect. The data were interpreted to suggest that in the telencephalon of the animals treated with PCPA-methyl ester, there was a higher turnover of 5-HT than was found in the saline-treated group. 相似文献
20.
Abstract— Pigeons working on a multiple lixed-ratio 50, fixed interval 10 schedule of food reinforcement were injected with l -tryptophan (300mg/kg; I.M.) and killed at various times before, during and after the period of behavioural depression following the administration of this amino acid (0, 25, 50, 90, 170 and 230 min). The levels of tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, tyrosine, dopamine and norepinephrine were concurrently measured in 4 specific areas of the brain (telencephalon, diencephalon plus mesencephalon, pons plus medulla-oblongata and cerebellum). The course of the increases in the level of 5-hydroxytryptamine in the telencephalon, and subsequent return to pre-injection levels, was temporally related to the onset of the decreased responding and gradual return to normal rates of responding. Changes in dopamine and norepinephrine were not correlated with the onset of and recovery from the decreased response rates. The data in this paper are discussed in terms of (a) the previously reported work with 5-hydroxytryptophan and (b) the importance of the telencephalic serotonergic system in certain types of behavioural depression. 相似文献