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41.
H. Rommelspacher Sabine Strau E. FÄhndrich H. J. Haug 《Journal of neural transmission (Vienna, Austria : 1996)》1987,69(1-2):85-96
Summary [3H] UK-14,304 was used to investigate
2-adrenoceptors in rat brain and human platelets. Receptor pharmacology revealed that the ligand binds with high affinity to
2-adrenoceptors. Psychoactive substances like neuroleptics, antidepressants, and-carbolines displace [3H] UK-14,304 from its binding sites in the lower micromolar range. A Hill number around 2 for most neuroleptics suggests a positive cooperativity with the
2-adrenoceptors.Comparative studies with [3H] UK-14,304 and [3H] clonidine utilizing platelet membranes from human volunteers demonstrated that the former ligand is more suitable to investigate possible changes of
2-adrenoceptors; [3H] UK-14,304 labels more receptors with a lower standard deviation, whereby the volume of the blood sample amounted to 35 ml instead of 50 ml required for [3H] clonidine as ligand. No sex differences of binding constants were detected, however an inverse correlation of maximum number of binding sites and affinity was found for female subjects with both ligands.No age-dependent changes of Bmax and KD-values were observed in the range of 24 to 59 years. 相似文献
42.
丹参和黄芪治疗气虚血瘀型心力衰竭的作用 总被引:2,自引:0,他引:2
本文报道91例气虚血瘀型心力衰竭(心衰)病人选用丹参和黄芪治疗作用。16例作气囊漂浮导管监测,发现黄芪明显增加心排出量、每搏量及心脏指数,而丹参无此作用,提示黄芪有正性肌力作用;30例给黄芪加党参,治疗后心功能分级及某些异常的血液流变学指标均有改善;44例先丹参,继之丹参加黄芪,治疗后心功能分级有明显改善,且能改善异常的血液流变学指标,明显抑制血小板聚集功能。提示丹参具有活血化瘀改善血液流变学及抑制血小板的聚集性,黄芪有补气强心改善心功能的作用。 相似文献
43.
Alain Segonzac Hans Schoemaker Christopher R. Lee Salomon Z. Langer 《Naunyn-Schmiedeberg's archives of pharmacology》1987,336(1):1-4
Summary 5-Methoxytryptoline (5-MeO-TLN, 6-methoxytetrahydro--carboline) inhibits with high affinity [3H]-imipramine binding to the serotonin transporter in platelets. To evaluate whether 5-MeO-TLN is a substrate for the serotonin transporter, the accumulation of [3H]-5-MeO-TLN into rabbit platelets was studied in vitro. At short incubation times (5 min), [3H]-5-MeO-TLN accumulation was temperature-sensitive, but not saturable over a concentration range from 0.06 mol/l to 10 mol/l Moreover, [3H]-5-MeO-TLN uptake was not affected by 100 mol/1 ouabain, its structural analogs tryptoline and 5-hydroxytryptoline, nor by the serotonin uptake inhibitors imipramine and citalopram. After longer incubation times (60 min), [3H]-5-MeO-TLN accumulation at O°C approached that seen at 37°C and temperature-sensitive [3H]-5-MeO-TLN uptake could no longer be observed. It is concluded that temperature-sensitive accumulation of [3H]-5-MeO-TLN is not mediated by the serotonin transporter and most likely represents a passive, diffusional process, the rate of which is temperature-dependent. The present studies thus confirm the hypothesis that 5-MeO-TLN affects [3H]-imipramine binding in platelets through a competitive mechanism and not via an allosteric interaction mediated through the substrate recognition site of the macromolecular complex of the serotonin transporter.
Send offprint requests to S. Z. Langer at the above address 相似文献
44.
Danka Peričié Hari Manev Sonja Levanat Branimi Jernej Dunja Vujić Nebojša Djordjević 《Psychopharmacology》1986,90(1):112-118
Acute (50.0 mg/kg) and repeated (0.1–10.0 mg/kg) administration of dihydroergosine (DHESN) to rats over 5 days lowered the concentration of 5-HIAA in the brain. DHESN given acutely increased the brain 5-HT in p-CPA-treated animals and diminished the probenecid-induced increase in brain 5-HIAA. In pargyline-treated rats DHESN enhanced the 5-HT/5-HIAA ratio. DHESN administered to rats repeatedly over 5 days decreased the level of 5-HT in blood platelets, and in vitro at concentrations of 10-4 M and 10-3 M inhibited the uptake of [14C]-5-HT in platelets. DHESN (10.0–100.0 mg/kg) potentiated the 5-HT syndrome produced in rats by pargyline and 5-HTP. This potentiation was blocked with cyproheptadine but not with haloperidol. DHESN (1.0 and 10.0 mg/kg) lowered the locomotor activity of rats and 10.0 mg/kg DHESN also reduced the duration of immobility in rats forced to swim in a restricted space. The results indicate that DHESN, like antidepressants, decreases the turnover of serotonin in the brain and potentiates the 5-HT-mediated behaviour. This might suggest that the drug should be further investigated for its potential antidepressive properties. 相似文献
45.
Summary The effects of several 5-carboxamide derivatives of adenosine on stimulatory (R
a) adenosine receptors of human platelets and inhibitory (R
i) adenosine receptors of rat fat cells have been compared. 5-N-Cyclopropylcarboxamidoadenosine (CPCA) and 5-N-ethylcarboxamidoadenosine (NECA) most potently inhibited ADP-induced aggregation of human platelets as shown by IC50-values of 0.24 and 0.34 mol/l. 5-N-Methylcarboxamidoadenosine (MECA; IC50 0.81 mol/l) and 5-N-carboxamidoadenosine (NCA; IC50 2.1 mol/l) were less potent, whereas adenosine, 2-chloroadenosine and (-)N6-phenylisopropyladenosine [(-)PIA] exhibit IC50-values of about 1.5 mol/l. Nearly the same rank order of potency was obtained for stimulation of adenylate cyclase activity of platelet membranes and for inhibition of [3H]NECA binding to human platelets. In order to examine the effects of the carboxamide analogues on R
i adenosine receptors of rat fat cells inhibition of lipolysis and adenylate cyclase were studied. (-)PIA was the most potent inhibitor of lipolysis as shown by an IC50 of 0.5 nmol/l, followed by CPCA (IC50 1.1 nmol/l) and NECA (IC50 1.3 nmol/l), whereas MECA (IC50 17.9 nmol/l) and NCA (IC50 20.1 nmol/l) were much less potent than NECA in inhibiting lipolysis. Similar results were obtained for inhibition of adenylate cyclase activity of fat cell membranes and for competition with [3H]PIA binding to fat cell membranes. The relative potencies of the adenosine analogues at both receptor subclasses were calculated from the ratio of the IC50-values for inhibition of platelet aggregation and of lipolysis. (-)PIA showed the highest selectivity for R
i
receptors as indicated by a 2,900-fold lower IC50 for the antilipolytic than for the antiaggregatory effect. The R
a/R
i activity ratio for NECA was about 260, for CPCA 220, for NCA 105 and for MECA 45. These results indicate that all 5-carboxamide adenosine derivatives are more potent agonists at R
i receptors than at R
a receptors. Since MECA has a higher selectivity for R
a receptors than NECA, it may be useful for the characterization of stimulatory adenosine receptors in different tissues. 相似文献
46.
47.
S. A. Pavlishchuk 《Bulletin of experimental biology and medicine》1979,88(6):1413-1416
The adhesive-aggregative activity of the platelets and the rate of blood clotting were compared in 125 healthy subjects during an emergency adaptation reaction (emotional stress, ACTH loading) and in 157 patients with heart and circulatory diseases during the period of crisis, and also during acute drug therapy. Changes in the platelets and plasma-coagulative components of hemostasis were found to be opposite in direction, and on this basis new ideas were put forward to explain the hemostatic function of the platelets.Department of Internal Medicine, Kuban Red Army Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 669–672, December, 1979. 相似文献
48.
Ferrarese C Zoia C Pecora N Piolti R Frigo M Bianchi G Sala G Begni B Riva R Frattola L 《Journal of neural transmission (Vienna, Austria : 1996)》1999,106(7-8):685-692
Summary. Defects in mitochondrial enzymes have been found not only in substantia nigra, but also in platelets from Parkinson's Disease
(PD) patients, suggesting a systemic impairment of energy metabolism. Since platelets present an energy-dependent glutamate
uptake similar to that described in central nervous system, glutamate uptake was determined in platelets from 34 PD patients
and 21 age-related normal controls, as Na+-dependent [3H]glutamate influx; glutamate level was also analyzed by reverse-phase HPLC. A 50% reduction of glutamate uptake (p < 0.001)
was observed in idiopathic PD patients, respect to controls and secondary parkinsonian syndromes. The decrease correlated
with the severity of PD, measured by the UPDRS (r = −0.54; P < 0.05). Glutamate level was increased in platelets of PD patients,
but was not correlated to the uptake decrease. Both phoenomena may be explained by the modifications of mitochondrial enzymes
described in platelets, which could be used as a peripheral model of glutamatergic function in PD.
Received October 7, 1998; accepted January 7, 1999 相似文献
49.
急性心肌梗死和稳定型心绞痛血小板GPⅡb,GPⅢa动态变化的比较研究 总被引:5,自引:0,他引:5
目的:观察急性心肌梗死(AMI)和稳定型心绞痛(SAP)血液中血小板表面糖蛋白GPⅡb和GPⅢa的动态变化,探讨急性心肌缺血前、后血小板的活性。方法:61例住院的心病患者,其中AMI32例,SAP29例,采用竞争性酶联免疫方法比较AMI及SAP患者发病后24h,第2天、第3天、1财2周时血中血汀反GPⅡb和GPⅢa的含量动态变化,并进行统计学分析,结果:SAP组GPⅡb和GPⅢa在上述5个时间段分 相似文献
50.
Reinhard Wölfel Karl-Heinz Graefe 《Naunyn-Schmiedeberg's archives of pharmacology》1992,345(2):129-136
Summary The aim of the present study was to answer the question whether amines other than 5-hydroxytryptamine (5-HT) and tryptamine act as substrates of the platelet 5-HT transporter. To this end, a large number of tryptamines, 5-HT receptor agonists and phenethylamines (which had IC50 values for 3H-5-HT uptake inhibition of 145–24500 nmol l–1) was examined in rabbit platelets in order to determine their ability to induce an outward transport of 3H-5-HT Platelets (the MAO of which was blocked) from reserpine-pretreated animals were loaded with 3H-5-HT and then exposed for 5 min to various concentrations (ranging from 0.25 to 40 times the IC50) of each compound. The concentration-effect curves for the drug-induced increase in 3H-5-HT efflux served to determine values of Emax (maximum increase in efflux expressed in % of the 3H-5-HT content of cells) and EC50 (drug concentration producing Emax/2).For the 24 compounds studied here (which included the 5-HT uptake inhibitors imipramine, citalopram, fluoxetine and cocaine) a linear correlation between EC50 and IC50 (r = 0.975) and a mean ratio of EC50/IC50 of 2.4 was found. Most of the compounds [e.g., (±)8-hy-ydroxy-2-(N,N-dipropylamino)tetralin, S(+)-methyl-5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine] gave rise to Emax values (15.8–32.5%) that exceeded that brought about by imipramine (6.6%), indicating that they act as substrates of the 5-HT transporter; the 3H-5-HT outward transport observed in response to these substances was abolished in the presence of imipramine. Others (e.g., 2-methyl-5-HT and 5-methylurapidil) produced Emax values (3.4–14.3%) not significantly different from that of imipramine and, therefore, can be classified either as poor substrates or as inhibitors of the 5-HT transporter.Hence, many tryptamines and 5-HT receptor agonists are substrates of the platelet 5-HT transporter. The property of being substrates gives them the latent capacity to bring about release of endogenous 5-HT and, as a result, to cause indirect 5-HT receptor-mediated effects.Abbreviations MAO
monoamine oxidase
- 5-HT
5-hydroxytryptamine
- 2-M-5-HT
2-methyl-5-HT
- N-M-5-HT
N-methyl-5-HT
- N,N-DM-5-HT
N,N-dimethyl-5-HT
- S(+)-M-5-HT
S(+)-methyl-5-HT
- 5-CT
5-carboxamidotryptamine
- 5-M-tryptamine
5-methyltryptamine
- 5-MO-tryptamine
5-methoxytryptamine
- 7-M-tryptamine
7-methyltryptamine
- N-M-tryptamine
N-methyltryptamine
- N,N-DM-tryptamine
N,N-dimethyltryptamine
- N,N-DM-5-MO-tryptamine
N,N-dimethyl-5-methoxytryptamine
- (±)8-OH-DPAT
(±)8-hydroxy-2-2-(N,N-dipropylamino)tetralin
- 5-M-urapidil
5-methyl-urapidil
Send offprint requests to R. Wölfel at the above address 相似文献