An analysis of the 5-hydroxytryptamine (serotonin) receptor subtypes of central neurones of Helix aspersa.

1. Intracellular recordings were made from identified neurones in the central nervous system of Helix aspersa. Two types of cell were used, those excited by 5-hydroxytryptamine (5-HT) and acetylcholine and those inhibited by 5-HT and dopamine. The actions of a range of 5-HT agonists and antagonists were tested for their ability to interact with 5-HT receptors. 2. 5-Carboxyamidotryptamine, alpha-methyl-5-HT and N-methyl-5-HT were active on cells excited by 5-HT, with similar potencies to 5-HT. Only 5-carboxyamidotryptamine and 5-methoxytryptamine were equiactive with 5-HT on cells inhibited by 5-HT. Most of the non-indole analogues were inactive or very weak agonists on both receptors. 3. MDL 72222 was the most active antagonist tested against 5-HT excitation, showing some selectivity for 5-HT over acetylcholine. Cinanserin and ketanserin also showed selectivity for 5-HT over acetylcholine. 4. Tryptamine was inhibitory on both cell types and was a potent antagonist of 5-HT excitation, showing selectivity for 5-HT over acetylcholine. 5. It is concluded that the 5-HT excitatory receptor recognizes the indole nucleus with substitution on position 5, save for 5-fluorotryptamine which was inhibitory. It does not appear that these 5-HT receptors can be classified in terms of the vertebrate subtypes of 5-HT receptor. However, it should be noted that only two receptor subtypes located on a small number of neurones were studied in these experiments and other 5-HT receptor suptypes may be located on other groups of neurones and peripheral tissues. These receptors may recognize other 5-HT receptor ligands including non-indoles.     

Effect of analogues of 5'-methylthioadenosine on cellular metabolism. Inactivation of S-adenosylhomocysteine hydrolase by 5'-isobutylthioadenosine.

The effects of a number of nucleosides related to 5'-methylthioadenosine on the activities of S-adenosylhomocysteine hydrolase, 5'-methylthioadenosine phosphorylase, spermidine synthase and spermine synthase were investigated. Both 5'-methylthioadenosine and 5'-isobutylthioadenosine gave rise to an enzyme-activated irreversible inhibition of S-adenosylhomocysteine hydrolase, but 5'-methylthiotubercidin (5'-methylthio-7-deaza-adenosine), 5'-deoxy-5'-chloroformycin, 5'-ethylthio-2-fluoro-adenosine and 1,N6-etheno-5'-methylthioadenosine were totally ineffective in producing this inactivation. Of the nucleosides tested, only 5'-methylthioadenosine, 5'-methylthiotubercidin and 5'-isobutylthioadenosine were inhibitory towards the aminopropyltransferases responsible for the synthesis of spermine and spermidine. 5'-Methylthiotubercidin, 5'-deoxy-5'-chloroformycin and 5'-isobutylthioadenosine were inhibitors of the degradation of 5'-methylthioadenosine by 5'-methylthioadenosine phosphorylase, but only 5'-isobutylthioadenosine was also a substrate for this enzyme. These results suggest that the effects of 5'-isobutylthioadenosine of the cell may result from the combination of inhibitory actions on polyamine synthesis, 5'-methylthioadenosine degradation and S-adenosylhomocysteine degradation. The resulting increased concentrations of S-adenosylhomocysteine could bring about inhibition of methyltransferase reactions. A new convenient method for the assay of S-adenosylhomocysteine hydrolase in the direction of synthesis is described.     

An analysis of the 5-hydroxytryptamine (serotonin) receptor subtypes of central neurones of Helix aspersa

1. Intracellular recordings were made from identified neurones in the central nervous system of Helix aspersa. Two types of cell were used, those excited by 5-hydroxytryptamine (5-HT) and acetylcholine and those inhibited by 5-HT and dopamine. The actions of a range of 5-HT agonists and antagonists were tested for their ability to interact with 5-HT receptors.2. 5-Carboxyamidotryptamine, α-methyl-5-HT and N-methyl-5-HT were active on cells excited by 5-HT, with similar potencies to 5-HT. Only 5-carboxyamidotryptamine and 5-methoxytryptamine were equiactive with 5-HT on cells inhibited by 5-HT. Most of the non-indole analogues were inactive or very weak agonists on both receptors.3. MDL 72222 was the most active antagonist tested against 5-HT excitation, showing some selectivity for 5-HT over acetylcholine. Cinanserin and ketanserin also showed selectivity for 5-HT over acetylcholine.4. Tryptamine was inhibitory on both cell types and was a potent antagonist of 5-HT excitation, showing selectivity for 5-HT over acetylcholine.5. It is concluded that the 5-HT excitatory receptor recognizes the indole nucleus with substitution on position 5, save for 5-fluorotryptamine which was inhibitory. It does not appear that these 5-HT receptors can be classified in terms of the vertebrate subtypes of 5-HT receptor. However, it should be noted that only two receptor subtypes located on a small number of neurones were studied in these experiments and other 5-HT receptor subtypes may be located on other groups of neurones and peripheral tissues. These receptors may recognize other 5-HT receptor ligands including non-indoles.     

BbRho5对球孢白僵菌生长速率的作用研究

为阐明BbRho5对球孢白僵菌生防潜能的作用,构建了Bbrho5单基因敲除菌株ΔBbrho5,以野生型菌株WT作为对照,在不同培养基上测定菌落生长速率,并测定了菌株对多菌灵胁迫耐受性及对大蜡螟幼虫体壁侵染能力。进一步获取和分析了ΔBbrho5和WT细胞内基因转录组数据。结果表明,BbRho5蛋白功能缺陷显著抑制球孢白僵菌菌丝生长速率,同时微弱影响其多菌灵胁迫抗逆性及生防能力。相较于WT,ΔBbrho5中具有770个差异表达基因(DEGs),其中上调基因395个,下调基因375个。GO分析显示,ΔBbrho5 VS WT中DEGs主要富集于氧化还原酶活力(oxidoreductase activity)和单加氧酶活力(monooxygenase activity)功能。KEGG通路富集结果显示,DEGs主要富集于氮代谢及多种氨基酸代谢通路。在氮代谢通路中富集到7个功能基因,其中有5个上调,2个下调,说明敲除菌株可能采用增强氮源利用及谷氨酸合成以应对Bbrho5缺陷引起的生长迟缓。以上研究结果揭示了球孢白僵菌中小GTP酶BbRho5对球孢白僵菌生长速率具有重要影响,且氮代谢和氨基酸代谢可能为其重要的响应代谢通路。     

BbRho5对球孢白僵菌生长速率的作用研究

为阐明BbRho5对球孢白僵菌生防潜能的作用,构建了Bbrho5单基因敲除菌株ΔBbrho5,以野生型菌株WT作为对照,在不同培养基上测定菌落生长速率,并测定了菌株对多菌灵胁迫耐受性及对大蜡螟幼虫体壁侵染能力。进一步获取和分析了ΔBbrho5和WT细胞内基因转录组数据。结果表明,BbRho5蛋白功能缺陷显著抑制球孢白僵菌菌丝生长速率,同时微弱影响其多菌灵胁迫抗逆性及生防能力。相较于WT,ΔBbrho5中具有770个差异表达基因(DEGs),其中上调基因395个,下调基因375个。GO分析显示,ΔBbrho5 VS WT中DEGs主要富集于氧化还原酶活力(oxidoreductase activity)和单加氧酶活力(monooxygenase activity)功能。KEGG通路富集结果显示,DEGs主要富集于氮代谢及多种氨基酸代谢通路。在氮代谢通路中富集到7个功能基因,其中有5个上调,2个下调,说明敲除菌株可能采用增强氮源利用及谷氨酸合成以应对Bbrho5缺陷引起的生长迟缓。以上研究结果揭示了球孢白僵菌中小GTP酶BbRho5对球孢白僵菌生长速率具有重要影响,且氮代谢和氨基酸代谢可能为其重要的响应代谢通路。     

Changes of Ganglioside Pattern During Cerebellar Development of Normal and Staggerer Mice

Saturable and specific binding sites for 5-[3H]hydroxytryptamine (5-HT, serotonin) characterized by a KD of 3.5-4.5 nM were detected in the chick embryo brain and were shown to develop linearly as a function of age, weight, and protein content. Saturation and displacement studies using unlabeled 5-HT as the displacing ligand suggested a single population of binding sites. However, displacement studies using 5-methoxytryptamine, lysergic acid diethylamide (LSD), 2-bromo-lysergic acid diethylamide (BOL), methysergide, and spiperone as competing ligands suggested the existence of subclasses of [3H]5-HT binding sites because the Hill coefficients were less than unity. When compared with the reported [3H]5-HT binding sites (5-HT1) in the rat forebrain, the IC50 values of the competing ligands were similar. However, the Hill coefficients for LSD and methysergide were less than unity which suggested that the [3H]5-HT binding sites in the chick embryo brain may be more similar to those found in rat spinal cord than rat forebrain. To study [3H]5-HT binding site regulation and development, various serotonergic compounds were injected into the chorioallantoic fluid of the eggs at different times during embryonic development. Multiple pretreatments with d,l-5-hydroxytryptophan, 5-HT, or BOL were found to have no significant effects on either the affinity (KD) or number (Bmax) of specific [3H]5-HT binding sites. Multiple pretreatments with p-chlorophenylalanine were found to increase the Bmax of specific [3H]5-HT binding by 23% (p less than 0.01) whereas multiple pretreatments with LSD were found to decrease the Bmax of specific binding by 45% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Respective role of each of the purine N7 nitrogens of 5'-O-triphosphoadenylyl(2'----5')adenylyl(2'----5')adenosine in binding to and activation of the RNase L of mouse cells

Through a combination of chemical and enzymatic approaches a series of sequence-specific tubercidin-substituted ppp5'A2'p(5'A2'p)n5'A (n = 1 to about 10; 2-5A) analogues were generated. In addition to the previously developed methodology of Imai and Torrence [Imai, J., & Torrence, P.F. (1985) J. Org. Chem. 50, 1418-1420], a new approach to synthesis of 2',5'-linked oligonucleotides utilized adenosine in 3',5' linkage as a precursor to the targeted 5'-terminus of the desired product. For instance, A3'p5'A could be condensed under conditions of lead ion catalysis with tubercidin 5'-phosphate to give A3'p5'A2'p5'(c7A). Treatment with the 3',5'-specific nuclease P1 led to p5'A2'p5'(c7A). The combined use of the above procedures led to the synthesis of p5'(c7A)2'p5'A2'p5'A, p5'A2'p5'(c7A)2'p5'A, p5'A2'p5'A2'p5'(c7A), and p5'A2p5'(c7A)2'p5'(c7A), which were converted to their corresponding 5'-triphosphates by the usual methods. Evaluation of these analogues for their ability to bind to and activate the 2-5A-dependent endonuclease (RNase L) of mouse L cells showed that there were small changes (less than or equal to 10-fold) in the ability of the four tubercidin analogues to bind to RNase L. However, whenever the first and/or third adenosine nucleotide units were replaced by tubercidin, a dramatic decrease in ability to activate RNase L occurred. Only the second (from the 5'-terminus) adenosine residue could be replaced by tubercidin without any effect on RNase L activation ability.     

Molecular Structure of Xanthocidin

In order to establish industrial production of 5′-inosinic acid (5′-IMP), a permeability mutant, KY13171, of Brevibacterium ammoniagenes, which accumulated 7 to 8 grams of 5′-IMP per liter and 4 to 6 grams of hypoxanthine (Hx) per liter (calculated as 5′-IMP), was improved by a genetical procedure. Further improved mutants were selected stepwise through repeating mutational work. The finally selected mutant. KY13369, accumulated 20 to 27 grams of 5′-IMP per liter, but not Hx.

Increased productivity of 5′-IMP and decreased productivity of Hx were not caused by the changes in 5′-IMP degrading activity, because these activities were not significantly different among the mutants. These results appear to indicate that the increased accumulation of 5′-IMP may be caused by the improvement in membrane permeability for 5′-IMP. However, the changes in phospholipid and fatty acid compositions were not enough to explain the increased permeability.     

Chemical synthesis and biological activities of analogues of 2',5'-oligoadenylates containing 8-substituted adenosine derivatives.

The synthesis of sequence-specific 2'-5'-oligonucleotides and analogues of 2'-5' linked oligoadenylates containing 8-substituted adenosine derivatives [8-hydroxypropyladenosine (AHPr) and 8-hydroxyadenosine (AOH)] is reported. The reaction of 5'-phosphoroimidazolidate of 8-substituted adenosines under conditions of lead ion catalyst did not give the corresponding 2'-5' oligoadenylates containing pAHPr and pAOH. When these reactions were carried out in the presence of uranyl ion (UO2(2+] in place of lead ion as a catalyst, the desired 2'-5' oligoadenylates were obtained. The p5'AHPr2'p5'AHPr2'p5'AHPr and p5'AOH2'p5'AOH2'p5'AOH, p5'A2'p5'A2'pAOH were slightly resistant to snake venom phosphodiesterase. The both circular dichroism and 1H-NMR spectra studies were used to characterize the modified 2'-5' oligoadenylates. Further, the biological activity evaluations of 8-substituted analogues of 2-5A are also described.     

A morphometric study of the protective effect of cryotherapy on oral mucositis in cancer patients treated with 5-fluorouracil

We investigated cytological changes in oral mucosa smears from patients treated with cryotherapy to determine whether cryotherapy prevented mucositis caused by 5-fluorouracil (5-FU) therapy. Patients with gastrointestinal malignancies were divided into four groups; control patients before 5-FU therapy, patients after 5-FU therapy without cryotherapy, patients with cryotherapy before 5-FU therapy and patients with cryotherapy after 5-FU therapy. Oral mucosa samples from all patients were assessed at the beginning and on day 14 of chemotherapy. We used exfoliative cytology to evaluate cellular changes in the oral mucosa that were caused by 5-FU. Smears from each patient were stained using the Papanicolaou method and analyzed using stereology. Smears were taken from each group before and after 5-FU infusion. We found that nuclear volume was decreased significantly in cells of the 5-FU therapy after cryotherapy patients compared to the 5-FU therapy before cryotherapy patients. We also found significantly decreased cytoplasmic volumes in the 5-FU therapy after cryotherapy patients compared to the 5-FU therapy before cryotherapy patients. The results of cytomorphometric estimations revealed that cryotherapy may be used to prevent damage to oral tissue and may decrease the frequency and duration of oral mucositis caused by 5-FU.     

Aminergic control of neuronal firing rate in thalamic motor nuclei of the rat

The effects induced on neuronal firing by microiontophoretic application of the biological amines noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were studied "in vivo" in ventral-anterior (VA) and ventrolateral (VL) thalamic motor nuclei of anaesthetized rats. In both nuclei the amines had a mostly depressive action on neuronal firing rate, the percentage of units responsive to NA application (88%) being higher than to 5-HT (72%). Short-lasting (less than 2 min) and long lasting (up to 20 min) inhibitory responses were recorded, the former mostly evoked by NA and the latter by 5-HT ejection. In some cases 5-HT application had no effect on the firing rate but modified the firing pattern. NA-evoked responses were significantly more intense in VL than in VA neurons. Short-lasting inhibitory responses similar to NA-induced effects were evoked by the alpha2 adrenergic receptor agonist clonidine and to a lesser extent by the beta adrenergic receptor agonist isoproterenol. Inhibitory responses to 5-HT were partially mimicked by application of the 5-HT(1A) receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) and of the 5-HT2 receptor agonist alpha-methyl-5-hydroxytryptamine (ALPHA-MET-5-HT). The latter evoked excitatory responses in some cases. Both 5-HT agonists were more effective on VA than on VL neurons. The effects evoked by agonists were at least partially blocked by respective antagonists. These results suggest that although both 5-HT and NA depress neuronal firing rate, their effects differ in time course and in the amount of inhibition; besides aminergic modulation is differently exerted on VA and VL.     

Enzymatic attack on side chains of synthetic polymers. Chymotrypsin-catalyzed hydrolysis of specific substrate groups attached to acrylamide or acrylic acid co-polymers.

Three vinyl monomers, M-1, M-3, and M-5, in which L-phenylalanine p-nitroanilide was acylated with CH2==CHCONH(CH2)nCO--(n = 1, 3, 5) were synthesized. They were co-polymerized with a large excess of acrylamide (co-polymers PAm-1, PAm-3, and PAm-5) and with a large excess of acrylic acid (co-polymers PAc=1, PAc-3, and PCc-5). In addition, M-5 was co-polymerized with acrylamide containing 2.8 mol % of the hydrophobic monomer N-acrylyl-1-naphthylamine (co-polymer PAm-5N). The rates of the chymotrypsin-catalyzed hydrolysis of the nitroanilide groups of M-5 and the various co-polymers were determined over a range of pH. For some of the systems data were also obtained over a range of substrate concentrations to derive values for Vmax and Km. Results obtained with PAm-5 were found to be independent of the chain length of the co-polymer. At pH 7, 25 degrees and with 2.7 X 10(-6) M enzyme, Vmax values for M-5, PAm-k, PAm-5N, and PAc-5 were 5.5, 5.5, 10, and 3.6 X 10(-8) M/S, while Km values were 8.5, 16.5, 10, and 2.2 X 10(-5),respectively, With PAc-5, the pH activity profile was shifted to higher acidities as compared to the profiles obtained with M-5 and PAm-5. The susceptibility of the co-polymers to chymotrypsin attack decreases sharply with a decreasing spacing of the L-phenylalanine p-nitroanilide residue from the backbone of the polymer chains.     

Effect of immobilization stress on serotonin content and turnover in regions of the rat brain.

Sprague-Dawley rats were stressed by immobilization from 30 to 300 minutes and the effects on serotonin (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) content were determined in the cerebral cortex, diencephalon, striatum, hippocampus and the brain stem. In a subsequent study 5-HT turnover rate in these brain areas was estimated by measuring 5-HIAA accumulation 0, 30, 60 and 90 minutes after probenecid. The content of 5-HIAA and the turnover rate of 5-HT were significantly increased in the cerebral cortex shortly after the onset of immobilization. The content of 5-HIAA in the brainstem was increased by immobilization although 5-HT turnover rate was not increased. Short term increases in 5-HIAA content were observed in the striatum and hippocampus. However, no significant changes in 5-HT turnover rate were observed in either of these 2 brain areas. Immobilization did not affect 5-HIAA content or 5-HT turnover in the diencephalon. The sensitivity of the serotonergic system in the cerebral cortex to immobilization stress suggests that this brain region could be used in future studies of the interrelationships between stress and the brain serotonergic system.     

奶牛乳铁蛋白基因5非翻译区PCR­SSCP多态性分析

采用PCR-SSCP技术,对奶牛乳铁蛋白基因5^'非翻译区1122bp序列进行多态性分析。在该区所划分的5个亚片段上,发现 Blf 5^'-1(227bp),Blf 5^'-3(175bp)和Blf 5^'-5（293bp）3个DNA片段存在多态。进一步对这3个片段进行测序分析,在Blf 5^'-1序列中,发现位于转录起始位点上游-926和-915位分别有G→A及T→G点突变;在Blf 5^'-3片段中,-478位存在G的插入;Blf 5^'-5位点上,发生-28位的C颠换为A和+33位的G颠换为C两处突变。利用TFSEARCH （ver.1.3）软件对乳铁蛋白基因5^'非翻译区潜在调控元件及蛋白质结合位点进行了预测,结果显示5^'非翻译区的突变引起了蛋白质结合因子的变化。     

The comparative effects of 5'-methylthioadenosine and some of its analogs on cells containing, and deficient in, 5'-methylthioadenosine phosphorylase

The antiproliferative effects of 5'-methylthioadenosine and the 5'-methylthioadenosine analogs, 5'-isobutylthioadenosine, 5'-deoxyadenosine and 5'-methylthiotubercidin were examined using two mouse cell lines, one 5'-methylthioadenosine phosphorylase-deficient the other containing 5'-methylthioadenosine phosphorylase. All of the compounds were found to be growth inhibitory to both cell lines, demonstrating that these compounds need not be degraded to exert their inhibitory effects. A correlation was observed between the potency of the growth inhibitory effect and the ability of the cells to degrade these compounds. 5'-Methylthioadenosine, 5'-deoxyadenosine and 5'-isobutylthioadenosine, all of which are substrates for the 5'-methylthioadenosine phosphorylase in vitro, were more growth inhibitory to the 5'-methylthioadenosine phosphorylase-deficient cells than to the 5'-methylthioadenosine phosphorylase-containing cells, whereas, the 7-deaza analog, 5'-methylthiotubercidin, a nondegradable inhibitor of the 5'-methylthioadenosine phosphorylase, was a more potent inhibitor of the 5'-methylthioadenosine phosphorylase-containing cell line. Due to the inhibition by 5'-methylthiotubercidin on 5'-methylthioadenosine phosphorylase in vitro the disposition of cellularly-synthesized 5'-methylthioadenosine was explored using both cell types. 5'-Methylthiotubercidin inhibited the accumulation of exogenous 5'-methylthioadenosine from 5'-methylthioadenosine phosphorylase-deficient cells with no effect on intracellular 5'-methylthioadenosine. In contrast, 5'-methylthiotubercidin caused a large accumulation of extracellular 5'-methylthioadenosine with a concomitant smaller increase intracellularly in 5'-methylthioadenosine phosphorylase-containing cells. That cellularly-synthesized 5'-methylthioadenosine as well as the cellular excretion of this nucleoside are altered in response to treatment with 5'-methylthiotubercidin suggests two possible sites at which 5'-methylthiotubercidin may exert its effect.     

Mechanism of action of serotonin on frog adrenal cortex

The mechanism of action of serotonin (5-HT) on frog adrenal cortex has been investigated in vitro using the perifusion system technique. The direct effect of 5-HT on corticosteroid secreting cells was demonstrated, using enzymatically dispersed adrenocortical cells. Melatonin and 5-HTP appeared to be less potent than 5-HT to enhance corticosteroid secretion. In contrast Trp and 5-HIAA were totally devoid of effect on steroid secretion. To investigate the type of receptor involved in the stimulatory effect of 5-HT on adrenocortical cells, adrenal slices were stimulated with 5-HT in absence or presence of various antagonists. We observed that classical antagonists of 5-HT1, 5-HT2 and 5-HT3 type receptors failed to block 5-HT-induced corticosteroid secretion in our model. These results show that 5-HT exerts a direct effect on corticosteroid-secreting cells. Our data also indicates that the type of receptor involved in the action of 5-HT in frog adrenal cortex differs from mammalian 5-HT receptors.     

Inhibition of M and P Phenol Sulfotransferase by Analogues of 3''-Phosphoadenosine-5''-Phosphosulfate

Structural analogues of the sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (3',5'-PAPS) were examined for their ability to inhibit dopamine and phenol sulfation by the M and P forms of phenol sulfotransferase (PST), respectively. The Ki values for each of the adenosine derivatives were calculated from the rate equation for PST. For both M and P PST, the naturally occurring product 3'-phosphoadenosine-5'-phosphate, (3',5'-PAP), was shown to be the most effective inhibitor. The weakest inhibitors of the two sulfotransferases were 5'-adenosine phosphosulfate and the three AMP derivatives, which were less than 1,000 times as effective as 3',5'-PAP. 5'-ATP, 2',5'-PAPS, 2',5'-PAP, and 5'-ADP were similar in their inhibition of M and P PST and were all approximately 100 times less effective than the natural end product. These data reveal that there is a rigid structural requirement for binding of the ribose portion of adenosine to both M and P PST that involves the groups on both the 3' and 5' positions. The effectiveness of binding to the two enzymes may depend on both steric factors as well as the distribution of negative charges on the ribose ring.     

Variations of enzyme activities in the haemocytes of scallop Chlamys farreri after infection with the acute virus necrobiotic virus (AVNV)

Acute virus necrobiotic virus (AVNV) is one of the main pathogens for large scale mortality of Chinese scallop Chlamys farreri. In this paper, C. farreri were infected by different dilutions of AVNV supernatant (5(0), 5(-1), 5(-2), 5(-3), 5(-4), 5(-5), 5(-6), 5(-7), respectively), and dead individuals were counted every day for 15 days. Samples from groups of 5(-3) and 5(-5) were taken every day till 15 days and the activities of acid phosphatase (ACP), alkaline phosphatase (ALP), superoxide dismutase (SOD), myeloperoxidase (MPO), phenoloxidase (PO), peroxidase (POD) and catalase (CAT) in haemocytes were measured. The results of virus challenge showed that survival rates of scallops in groups of 5(0) and 5(-1) decreased sharply after the first day and died out completely on the 5th and 4th day, respectively. In other groups (5(-2), 5(-3), 5(-4), 5(-5), 5(-6) and 5(-7)), survival rates decreased gradually till 6 or 7 days, then kept steady till 15 days, and they were dose-dependent, increasing from 12% to 80% as the dose decreased from 5(-2) to 5(-7) viral supernatant. In the control group, survival rate was 88%. Enzyme activities for groups of 5(-3) and 5(-5) illustrated that activities of ACP, SOD, MPO, PO in groups of 5(-3) and 5(-5) were significantly higher than the control group in the first 9 or 10 days, and went back to the control group levels gradually after 10 days. Moreover, their activities in group of 5(-3) varied more than that in the group of 5(-5), especially activities of MPO, PO. Differently, the activities of POD and CAT were reduced or induced by virus infection and showed no regular trends in the experiments. The activity of ALP was not detected.     

Activation of peripheral serotonin2 receptors induces hypothermia in mice

The effects of peripherally administered serotonin (5-HT) on the rectal temperature were investigated. 5-HT i.p. induced a dose-dependent hypothermia in mice. The hypothermic effects of 5-HT were strongly antagonized by the 5-HT1 and 5-HT2 receptor antagonist methysergide and the 5-HT2 receptor antagonist ketanserin. However, the 5-HT1 receptor antagonist pindolol and the 5-HT3 receptor antagonist ICS 205-930 were without effect. In addition, the peripheral 5-HT2 receptor antagonist xylamidine strongly reduced 5-HT-induced hypothermia. These results indicate that the activation of the peripheral 5-HT2 receptors induces hypothermia, although the central 5-HT2 receptors have been suggested to relate to hyperthermia.     

Effects of acute and chronic administrations of phencyclidine on the levels of serotonin and 5-hydroxyindoleacetic acid in discrete brain areas of mouse

The effects of phencyclidine (PCP) on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain areas of mouse were investigated. Following a single administration, PCP significantly increased at 60 min the level of 5-HT but not 5-HIAA in the cortex. However, acute administration of PCP induced no changes of 5-HT and 5-HIAA levels in other brain areas investigated. On the other hand, chronic treatment of PCP produced a significant increase the striatal 5-HT and 5-HIAA levels by about 30% and 20%, respectively. These increased levels were gradually returned to the control levels, and there was no difference of these levels between the control group and the 48 hr withdrawal group. The changes of 5-HT level in the hypothalamus were similar to those in the striatum. These results suggest that the pharmacological actions of PCP and tolerance development to PCP may be related to the functional changes of serotonergic neuronal activity.