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101.
Peter Molenaar Grant A. McPherson Errol Malta Colin Raper 《Naunyn-Schmiedeberg's archives of pharmacology》1985,331(2-3):240-246
Summary The affinity and efficacy of a number of sympathomimetic amines structurally related to prenalterol and the selective 1-adrenoceptor agonist RO 363 were determined using a combination of radioligand binding and organ bath techniques. Affinity of the molecules (pK
D) was calculated from their ability to displace the radioligand [125I]iodocyanopindolol ([125I]CYP) from -adrenoceptor sites in left atrial (1) and uterine (2) membrane homogenates. These pK
D values were used to calculate efficacy from the positive inotropic and uterine relaxant responses elicited by the drugs in organ bath experiments. The drugs studied were either arylethanolamines i.e., (–)-isoprenaline (ISO), p-hydroxyisoprenaline (pOH-ISO), compounds XIV and XVI or aryloxypropanolamine-derivatives, i.e., oxymethylene-isoprenaline (OM-ISO), prenalterol and Compound XI which possessed ap-phenol or catechol ring and an isopropyl or a homoveratryl amine substituent. Only ISO, OM-ISO, pOH-ISO and Compound XVI were active as agonists in both tissue preparations. These drugs were partial agonists which exhibited a wide range of pD2 values and did not display any marked selectivity for either -adrenoceptor subtype. Compound XI and prenalterol were inactive as agonists and together with the partial agonists behaved as competitive antagonists to ISO in the two preparations. All drugs tested displaced [125I]CYP from -adrenoceptor sites, however, there was also a wide range of potency amongst the drugs.Analysis of the structure-affinity and structure-efficacy relationships indicated that removal of the 3-hydroxyl group from the catechol ring reduces both affinity and efficacy without altering the selectivity of the drug for either -adrenoceptor subtype. While aryloxypropanolamine derivatives have generally higher affinities than arylethanol-amines, especially at -adrenoceptor sites, their efficacies are generally reduced at both -adrenoceptors. The presence of a homoveratryl group in aryloxypropanolamines enhances slightly the affinity for 1- and reduces affinity for 2-adrenoceptors. With this amine group, efficacy is markedly reduced at 2- as opposed to 2-adrenoceptor sites.Thus for prenalterol, the small degree of cardioselectivity can be attributed to the oxymethylene group whilst its lack of agonist activity (i.e., efficacy) reflects a combined action of this group and the absence of the 3-hydroxyl group on the phenyl ring. In RO363 it can be deduced that the oxymethylene group, together with the homoveratryl substituent are responsible for the observed selective affinity of the drug for 1- as opposed to 2-adrenoceptors. 相似文献
102.
The hypothermic and motor behavioural responses to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) have been investigated in the rat. The dose-effect relationship showed that hypothermia appeared at a lower dose than a definite motor syndrome. The hypothermic response to 8-OH-DPAT was attenuated following depletion of 5-hydroxytryptamine (5-HT) by repeated intraperitoneal (IP) administration of parachlorophenylalanine (200 mg/kg) or by injection of 5,7-dihydroxytryptamine (5,7-DHT, 100 g) into the region of the third ventricle; the motor behavioural response produced simultaneously was not. Indeed, after 5,7-DHT, it was increased. Quipazine (1 mg/kg, IP) antagonised the hypothermic response and facilitated the motor behaviour. Clenbuterol (2.5 mg/kg, IP) increased both hypothermic and motor responses. (±)-propranolol was without effect on the simple hypermotility produced by 8-OH-DPAT, although it is known to antagonise the hypothermic and stereotyped motor responses. It is concluded that 8-OH-DPAT probably produces its hypothermic effects by actions at 5-HT receptors located presynaptically on 5-HT neurones, while the stereotyped components of the serotonin syndrome appear to be mediated by post-synaptic receptors. 相似文献
103.
Olof Beck Kym F. Faull David B. Repke 《Naunyn-Schmiedeberg's archives of pharmacology》1986,333(3):307-312
Summary Racemic methtryptoline (1-methyltetrahydro--carboline) and 5-hydroxymethtryptoline-9-carboxylic acid (6-hydroxy-1-methyltetrahydro--carboline-1-carboxylic acid) were administered intraperitoneally to rats and the components of their urine was subsequently investigated by chiral gas chromatography-mass spectrometry. Methtryptoline rapidly became hydroxylated in the 5- and 6-position and excreted in urine. There was about a ninefold predominance of the S(–) enantiomer over the other in the 5-hydroxylated species, while the 6-hydroxylation produced a small excess of the R(+) enantiomer. About 75% of the injected dose of methtryptoline was recovered in the urine as 5- and 6-hydroxylated compounds during the first 24 h period, demonstrating that hydroxylation represents the major metabolic pathway. Treatment with 6-hydroxymethtryptoline-9-carboxylic acid led to a fivefold increase in the urinary excretion of 5-hydroxymethtryptoline during the first 24 h period with a predominance of the S(–)-enantiomer, indicating a much smaller conversion rate than from methtryptoline. It was concluded that hydroxylation of methtryptoline is a likely pathway for the natural formation of 5-hydroxymethtryptoline. 相似文献
104.
The analgesic ED50 values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain d-amino acid in position 2 and d- or l-sulfonic (or phosphonic) acid residue in position 5). -Endorpin, d-Met2, Pro5-enkephalinamide and two partial agonists showed intermediate interspecies relative potencies. According to the data obtained, similar opiate receptors might mediate the analgesic action of classical opiates in rats and in mice. However, the opiate receptors responsible for the antinociceptive effects of the above mentioned enkephalin analogues must be dissimilar in the two species examined. The results are discussed in terms of the role of - and -receptors in mediation of the analgesic effect induced by different types of opioids. 相似文献
105.
H. Hall S. B. Ross Maria Sällemark 《Journal of neural transmission (Vienna, Austria : 1996)》1984,59(1):9-23
Summary The dependence of intact noradrenergic and serotonergic nerve terminals for the decrease in the number of-adrenoceptors and 5-HT2 binding sites in the cerebral cortex produced by long-term treatment of rats with antidepressant drugs was examined. Noradrenergic nerve terminals were destroyed with the selective noradrenaline neurotoxin DSP4, and serotonergic nerve terminals were destroyed with p-chloroamphetamine (PCA). It was found that lesioning of the noradrenergic nerve terminals abolished the decrease in-adrenoceptors produced by desipramine, mianserin and zimeldine and partially antagonized that of the-adrenoceptor agonist clenbuterol. PCA pretreatment did not antagonize the long-term effects on the-adrenoceptor produced by these compounds.Lesioning of serotonergic nerve terminals affected the down-regulation of 5-HT2 binding sites produced by long-term treatment with mianserin, desipramine and amiflamine. DSP4 pretreatment partially abolished the down-regulation of 5-HT2 binding sites produced by long-term treatment with desipramine, while the effects of mianserin and amiflamine were unaffected by pretreatment with DSP4. 相似文献
106.
青岛大学附属烟台毓璜顶医院生殖医学中心对1例反复体外受精/卵细胞质内单精子注射(IVF/ICSI)助孕后早期胚胎发育停滞的患者进行了全外显子基因检测,发现了一种新的TUBB8基因突变型(c.208C>T/p.Pro70Ser),并进一步探讨了TUBB8基因突变与早期胚胎发育停滞之间的联系,为反复种植失败的诊断与治疗提供更多可能性。 相似文献
107.
Kim Han Komudi Singh Matthew J. Rodman Shahin Hassanzadeh Yvonne Baumer Rebecca D. Huffstutler Jinguo Chen Julin Candia Foo Cheung Katherine E. R. Stagliano Mehdi Pirooznia Tiffany M. Powell-Wiley Michael N. Sack 《Nutrients》2021,13(5)
Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects’ blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4+ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4+ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4+ T cell immune responsiveness. 相似文献
108.
Franois-Xavier Briand Eric Niqueux Audrey Schmitz Claire Martenot Martine Cherbonnel Pascale Massin Florian Kerbrat Marina Chatel Carole Guillemoto Cecile Guillou-Cloarec Katell Ogor Aurlie Le Prioux Chantal Alle Vronique Beven Edouard Hirchaud Yannick Blanchard Axelle Scoizec Sophie Le Bouquin Nicolas Eterradossi Batrice Grasland 《Emerging infectious diseases》2021,27(2):508
We detected 3 genotypes of highly pathogenic avian influenza A(H5N8) virus in France during winter 2016–17. Genotype A viruses caused dramatic economic losses in the domestic duck farm industry in southwestern France. Our phylogenetic analysis suggests that genotype A viruses formed 5 distinct geographic clusters in southwestern France. In some clusters, local secondary transmission might have been started by a single introduction. The intensity of the viral spread seems to correspond to the density of duck holdings in each production area. To avoid the introduction of disease into an unaffected area, it is crucial that authorities limit the movements of potentially infected birds. 相似文献
109.
目的 :探讨新生儿高间接胆红素血症 (高间胆 )血清中白细胞介素 6 (IL- 6 )及白细胞介素 8(IL- 8)水平变化及其意义。方法 :采用 EL ISA法对住院的高间胆病婴的感染组 (A组 )和非感染组 (B组 )以及对照组进行血清 IL- 6、 IL- 8及胆红素的检测 ,比较各组的胆红素、IL- 6、IL- 8水平 ,黄疸消退前后 IL- 6、IL- 8水平 ,并进行相关因素的分析。结果 :A组总胆红素 (344 .0 3± 74.5 ) μmol/ L,较 B组高 [(2 77.83± 45 .12 ) μm ol/ L],间接胆红素 (间胆 ) (32 2 .9± 72 .12 ) μm ol/ L,较B组高 [(2 5 4.2 9± 44 .8) μmol/ L],A、 B两组 IL- 6分别为 (10 1.6 2± 38.77) ng/ L、 (75 .13± 13.77) ng/ L,均显著高于对照组 [(30 .6 6± 3.17) ng/ L],A、B两组 IL- 8分别为 (190 .0 2± 5 9.0 3) ng/ L 及 (15 0 .5 4± 2 5 .6 2 ) ng/ L,均显著高于对照组 [(10 8.30± 7.37) ng/ L];两组黄疸消退前后的 IL- 6及 IL- 8比较有显著性差异 (P <0 .0 0 1) ,多因素相关分析 ,IL- 6与感染因素密切相关 (P <0 .0 1) ,IL- 8与间胆呈正相关 (P <0 .0 0 1)。结论 :IL- 6及 IL- 8水平高低可作为高间胆病因及免疫自损程度诊断手段之一。 相似文献
110.
目的探讨血清新蝶呤、sCD4及sCD8分子水平和鼻咽癌的关系及临床意义。方法采用ELISA方法检测54例初治鼻咽低分化鳞癌治疗前、后及32例健康成人的血清新蝶呤、sCD4与sCD8分子浓度。结果鼻咽癌血清新蝶呤、sCD4及sCD8浓度高于健康对照组(P<0.001)。不同TNM分期血清新蝶呤、sCD4及sCD8水平无差异(P>0.05);无淋巴结转移者血清新蝶呤低于有淋巴结转移者(P<0.05)。治疗后新蝶呤、sCD4与sCD8水平比治疗前明显降低(P<0.01),仍比对照组高(P<0.01);治疗后6月肿瘤全消者继续保持在较低水平,肿瘤残留者则回升到治疗前水平(P<0.01和0.05)。结论血清新蝶呤、sCD4与sCD8分子水平检测可作为鼻咽癌病情评估、疗效监测及随访的客观指标。 相似文献