Pharmacology & toxicology最新文献_第3页

Modulation of contractile force by endothelin receptors in porcine myocardial trabeculae. 内皮素受体对猪心肌小梁收缩力的调节。

Pharmacology & toxicology Pub Date : 2000-10-01 DOI: 10.1034/j.1600-0773.2000.d01-72.x

O Saetrum Opgaard, B Tom, R de Vries, L Edvinsson, P R Saxena

{"title":"Modulation of contractile force by endothelin receptors in porcine myocardial trabeculae.","authors":"O Saetrum Opgaard, B Tom, R de Vries, L Edvinsson, P R Saxena","doi":"10.1034/j.1600-0773.2000.d01-72.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-72.x","url":null,"abstract":"The aim of the study was to determine possible inotropic effects mediated by endothelin-A and endothelin-B receptors in porcine myocardial trabeculae from right atria and left ventricles. Isolated trabeculae were paced at 1.5 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. Endothelin-1 and endothelin-3 had a strong and potent positive inotropic effect in all trabeculae. In all atrial and in some ventricular trabeculae this effect was preceded by a transient negative inotropic effect at 10(-7) M. The endothelin-B receptor agonist IRL 1620 had a positive inotropic effect in some of the ventricular trabeculae, and no negative inotropic effect. Another endothelin-B receptor agonist, sarafotoxin S6c, had no positive inotropic effect, but induced a transient negative inotropic effect in some atrial trabeculae at 10(-7) M. In atrial trabeculae the preincubation with the endothelin-A receptor antagonist FR139317 (10(-6) M) decreased significantly (P<0.01) the maximum positive inotropic responses and abolished negative inotropic responses to endothelin-1. In conclusion, both endothelin-A and endothelin-B receptors may have the potential to mediate both positive and negative inotropic responses, but a positive inotropic effect mediated mainly via endothelin-A receptors seems to predominate.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"87 4","pages":"185-92"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21921493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mycophenolate mofetil pharmacokinetics in transplant patients receiving cyclosporine or tacrolimus in combination therapy. 接受环孢素或他克莫司联合治疗的移植患者霉酚酸酯的药代动力学。

Pharmacology & toxicology Pub Date : 2000-10-01 DOI: 10.1034/j.1600-0773.2000.d01-71.x

E Vidal, C Cantarell, L Capdevila, V Monforte, A Roman, L Pou

{"title":"Mycophenolate mofetil pharmacokinetics in transplant patients receiving cyclosporine or tacrolimus in combination therapy.","authors":"E Vidal, C Cantarell, L Capdevila, V Monforte, A Roman, L Pou","doi":"10.1034/j.1600-0773.2000.d01-71.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-71.x","url":null,"abstract":"Mycophenolate mofetil is a highly effective immunosuppressant drug used in the prophylaxis of organ rejection in combination with cyclosporine or tacrolimus and corticosteroids. The present study is a retrospective data analysis of the routinely estimated mycophenolic acid plasma trough levels in 60 transplant patients (kidney, n = 49; lung, n = 11) receiving mycophenolate mofetil in combination with prednisone and cyclosporine (n = 45) or tacrolimus (n = 15). Coadministration of cyclosporine instead of tacrolimus resulted in a significant increase of median (range) of the ratio of dose-to-concentration 0.92 (0.11-8.33) (n=167) versus 0.38 (0.11-14.28) (n = 66); P < 0.0001. No correlation was seen between mycophenolate mofetil dose and mycophenolic acid trough concentrations. The dose-to-concentration in cyclosporine-treated patients increased significantly (P<0.0001) as the cyclosporine level increased, suggesting a possible interaction between mycophenolate mofetil and cyclosporine. No correlation was seen between dose-to-concentration and tacrolimus blood levels (P x 0.215). Further studies are necessary to investigate this issue.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"87 4","pages":"182-4"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21921553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 33

Lindane (gamma-hexachlorocyclohexane) induces internal Ca2+ release and capacitative Ca2+ entry in Madin-Darby canine kidney cells. 林丹(γ -六氯环己烷)诱导Madin-Darby犬肾细胞内Ca2+释放和Ca2+进入。

Pharmacology & toxicology Pub Date : 2000-10-01 DOI: 10.1034/j.1600-0773.2000.d01-65.x

C H Lu, K C Lee, Y C Chen, J S Cheng, M S Yu, W C Chen, C R Jan

{"title":"Lindane (gamma-hexachlorocyclohexane) induces internal Ca2+ release and capacitative Ca2+ entry in Madin-Darby canine kidney cells.","authors":"C H Lu, K C Lee, Y C Chen, J S Cheng, M S Yu, W C Chen, C R Jan","doi":"10.1034/j.1600-0773.2000.d01-65.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-65.x","url":null,"abstract":"The effect of lindane (gamma-hexachlorocyclohexane), an organochlorine pesticide, on Ca2+ mobilization in Madin-Darby canine kidney cells was examined by fluorimetry using fura-2 as a Ca2+ indicator. Lindane (5-200 microM) increased [Ca2+]i concentration-dependently. The [Ca2+]i signal comprised an immediate initial rise followed by a persistent phase. Ca2+ removal inhibited the [Ca2+]i signal by reducing both the initial rise and the sustained phase. This implies lindane-triggered Ca2+ influx and Ca2+ release. In Ca2+ -free medium, 0.15 mM lindane increased [Ca2+]i after pretreatment with carbonylcyanide m-chlorophenylhydrazone (CCCP, 2 microM), a mitochondrial uncoupler, and two endoplasmic reticulum Ca2+ pump inhibitors, thapsigargin and cyclopiazonic acid. Conversely, pretreatment with lindane abolished CCCP- and thapsigargin-induced Ca2+ release. This suggests that 0.15 mM lindane released Ca2+ from the endoplasmic reticulum, mitochondria and other stores. La3+ (1 mM) partly inhibited 0.1 mM lindane-induced [Ca2+]i increase, confirming that lindane induced Ca2+ influx. Addition of 3 mM Ca2+ increased [Ca2+]i after pretreatment with 0.15 mM lindane for 750 sec. in Ca2+ -free medium, which indicates lindane-induced capacitative Ca2+ entry. Lindane (0.15 mM)-induced Ca2+ release was not reduced by inhibiting phospholipase C with 2 microM U73122, but was inhibited by 70% by the phospholipase A2 inhibitor aristolochic acid (40 microM).","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"87 4","pages":"149-55"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21921697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Anticipation of acute stress in isoprenaline-sensitive and - resistant rats: strain and gender differences. 异丙肾上腺素敏感和耐药大鼠的急性应激预期:品系和性别差异。

Pharmacology & toxicology Pub Date : 2000-10-01 DOI: 10.1034/j.1600-0773.2000.d01-67.x

A Yamamotová, M Starec, V Holecek, J Racek, L Trefil, H Rasková, R Rokyta

{"title":"Anticipation of acute stress in isoprenaline-sensitive and - resistant rats: strain and gender differences.","authors":"A Yamamotová, M Starec, V Holecek, J Racek, L Trefil, H Rasková, R Rokyta","doi":"10.1034/j.1600-0773.2000.d01-67.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-67.x","url":null,"abstract":"The effect of stress anticipation was studied in two inbred Wistar rat strains with high and low sensitivity to isoprenaline. The animals were exposed to tail-flick and 4-hr water immersion restraint stress on two consecutive days. On the first day stress was applied to one group and the next day to the anticipation group. The changes in adrenal, heart and spleen weights, tail-flick latency, incidence of gastric ulcers, and the antioxidant defense system in the sensorimotor cortex were compared with two non-stressed control groups. Anticipatory stress decreased adrenal weights. The content of thiobarbituric acid reactive substances (TBARS) was increased both in acute and anticipatory stress; superoxide dismutase, glutathione peroxidase, and antioxidative capacity were increased in anticipatory stress only. Stress anticipation decreased the pain threshold in the isoprenaline-sensitive and increased in the isoprenaline-resistant rats and led to more frequent gastric ulcers in the isoprenaline-resistant group. Significant sex differences were observed both in adrenal weights and TBARS content. The relative adrenal weights were negatively correlated with the TBARS content. We suggest that the outcome of anticipatory stress may depend upon the relation between the hormonal and antioxidant functions of the adrenals and that anticipation-induced activation of antioxidant enzymes may ameliorate the acute stress response. Anticipation itself was found to be a stronger stressor than physical acute stress.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"87 4","pages":"161-8"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21921543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Mobilisation of cadmium by meso- and racemic-2,3-dimercaptosuccinic acid (DMSA) in rats. 中位和外消旋-2,3-二巯基琥珀酸(DMSA)对大鼠镉的动员作用。

Pharmacology & toxicology Pub Date : 2000-10-01 DOI: 10.1034/j.1600-0773.2000.d01-70.x

M Blanusa, K Kostial, N Restek-Samarzija, M Piasek, M M Jones, P K Singh

{"title":"Mobilisation of cadmium by meso- and racemic-2,3-dimercaptosuccinic acid (DMSA) in rats.","authors":"M Blanusa, K Kostial, N Restek-Samarzija, M Piasek, M M Jones, P K Singh","doi":"10.1034/j.1600-0773.2000.d01-70.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-70.x","url":null,"abstract":"A higher efficiency of cadmium binding with racemic than with meso-2,3-dimercaptosuccinic acid (rac-DMSA; meso-DMSA) was found in an in vitro speciation model by Fang et al. (1996). This finding has not yet been tested in vivo. This paper presents results on mobilisation of cadmium by meso- and rac-DMSA in rats. Cadmium chloride was administered as the radioactive isotope 109Cd intraperitoneally to all animals. One group was an untreated control and two groups were treated with meso- and rac-DMSA, respectively. Treatment with chelators was applied twice, immediately after 109Cd and 24 hr afterwards intraperitoneally at the dose of 1 mmol/kg, each. Six days later radioactivity was measured in the liver and kidneys. Whole-body counting was carried out on days 1, 2, 3 and 6 of the experiment. At the end of the experiment, both treatments caused a decrease in 109Cd whole-body retention with rac-DMSA being more efficient (decrease from 83% in control to 74% and 64% in groups treated with meso- and rac-DMSA, respectively). The same reduction of 109Cd was obtained by both chelators in the liver (from 57% to about 47%). In the kidney only rac-DMSA produced significant reduction of 109Cd (from 5.3% to 3.5%). In conclusion, these results show modest reduction of cadmium in the body by two isoforms of DMSA with rac-DMSA being slightly more efficient than meso-DMSA.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"87 4","pages":"179-81"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21921552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

2-Phenylmelatonin: a partial agonist at enteric melatonin receptors. 2-苯褪黑素:肠道褪黑素受体的部分激动剂。

Pharmacology & toxicology Pub Date : 2000-10-01 DOI: 10.1034/j.1600-0773.2000.d01-66.x

M G Santagostino-Barbone, E Masoero, V Spelta, A Lucchelli

{"title":"2-Phenylmelatonin: a partial agonist at enteric melatonin receptors.","authors":"M G Santagostino-Barbone, E Masoero, V Spelta, A Lucchelli","doi":"10.1034/j.1600-0773.2000.d01-66.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-66.x","url":null,"abstract":"The effect of the melatonin receptor ligand, 2-phenylmelatonin, has been assessed in isolated strips of the guinea-pig proximal colon. 2-Phenylmelatonin (0.01 nM-1 microM) caused a concentration-dependent contractile response. The potency value (-log EC50) was 9.3 +/- 1.0. The maximum effect was 25 +/- 4%, of that elicited by the maximally effective concentration (0.3 microM) of 5-HT and 43 +/- 3%, of that by the maximally effective concentration (10 microM) of melatonin. When used as an antagonist, 2-phenylmelatonin (0.01 nM and 0.1 nM) concentration-dependently inhibited melatonin-induced contractions with depression of the maximum response by 25% and 54%, respectively. Higher (1 nM) 2-phenylmelatonin concentrations failed to antagonize melatonin-induced response. Prazosin (0.3 microM), a selective antagonist of melatonin MT3 sites, antagonized melatonin-induced contractions to an extent similar to that induced by 0.01 nM 2-phenylmelatonin (with 30% reduction of the maximum effect to melatonin). The combination of 0.3 microM prazosin and 0.01 nM 2-phenylmelatonin caused antagonism similar in extent to that caused by each individual antagonist. 2-Phenylmelatonin at subnanomolar concentrations behaves as an antagonist of melatonin-induced contractile responses while at nanomolar/micromolar concentrations it behaves as a weak contractile agonist.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"87 4","pages":"156-60"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21921542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Expression changes of CYP2A and CYP3A in microsomes from pig liver and cultured hepatocytes. 猪肝脏和培养肝细胞微粒体中CYP2A和CYP3A的表达变化。

Pharmacology & toxicology Pub Date : 2000-10-01 DOI: 10.1034/j.1600-0773.2000.d01-69.x

M T Skaanild, C Friis

引用次数: 0

Antinociceptive effect of intracerebroventricular administration of cholecystokinin antagonist in nerve-ligated mice. 神经结扎小鼠脑室内给药胆囊收缩素拮抗剂的抗痛觉作用。

Pharmacology & toxicology Pub Date : 2000-10-01 DOI: 10.1034/j.1600-0773.2000.d01-68.x

M R Zarrindast, F Samiee, M Rezayat

引用次数: 1

Doses and time-dependent effects of 3'-azido-3'-deoxythymidine on T47D human breast cancer cells in vitro. 3'-叠氮-3'-脱氧胸腺嘧啶对T47D人乳腺癌细胞的剂量及时间依赖性研究

Pharmacology & toxicology Pub Date : 2000-09-01 DOI: 10.1111/j.0901-9928.2000.870307.x

M D Mediavilla, E J Sánchez-Barceló

{"title":"Doses and time-dependent effects of 3'-azido-3'-deoxythymidine on T47D human breast cancer cells in vitro.","authors":"M D Mediavilla, E J Sánchez-Barceló","doi":"10.1111/j.0901-9928.2000.870307.x","DOIUrl":"https://doi.org/10.1111/j.0901-9928.2000.870307.x","url":null,"abstract":"The objective of the present work was to study the effects of 3'-azido-3'-deoxythymidine (azidothymidine, Zidovudine) on human breast cancer cells by using, as a model, the T47D cell line (typified as oestrogen-dependent and p53-mutated). Low azidothymidine doses (3.125 microM) increase the percentage of cells in S-phase, with the effect reversing after 24 hr of incubation; as azidothymidine doses increase, the magnitude and duration of its effect increase proportionally, although, even with the highest concentrations (50-100 microM) the effects decline after 48 hr of incubation. If media (containing azidothymidine or vehicle) are daily renewed, the azidothymidine effects (accumulation of cells in S-phase) are higher and decline later than when media and drug are not changed during the whole culture period, thereby suggesting that the reversion of azidothymidine effects could be related with a degradation of the drug or accumulation in media of substances which counteract its effects. Azidothymidine inhibits T47D cell proliferation at concentrations higher than 50 microM. The exposure to 50 or 100 microM azidothymidine induced cell apoptosis after 48 hr or more of incubation. We conclude that: a) azidothymidine, with appropriate doses and duration of treatment, synchronizes cells in S-phase, inhibits proliferation, and induces apoptosis, b) the discontinuous application of the drug rather than continuous exposure to it increases its efficiency to synchronize the T47D cell cycle. This in vitro anti-breast cancer activity suggests that a possible clinical usefulness of azidothymidine, either alone or associated with other drugs with cycle-specific antitumoural activity circumscribed to the S-phase of cell cycle, is worthy of investigation.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"87 3","pages":"138-43"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21894087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Effect of imipramine on tolerance to morphine antinociception in the formalin test. 丙咪嗪对福尔马林试验吗啡耐受性的影响。

Pharmacology & toxicology Pub Date : 2000-09-01 DOI: 10.1111/j.0901-9928.2000.870306.x

M R Zarrindast, S Shaverdian, M Sahebgharani

{"title":"Effect of imipramine on tolerance to morphine antinociception in the formalin test.","authors":"M R Zarrindast, S Shaverdian, M Sahebgharani","doi":"10.1111/j.0901-9928.2000.870306.x","DOIUrl":"https://doi.org/10.1111/j.0901-9928.2000.870306.x","url":null,"abstract":"In this study, the effect of imipramine on morphine antinociception in tolerant and non-tolerant mice in the formalin test, was investigated. Subcutaneous administration of different test doses of morphine (3, 6 and 9 mg/kg) and intraperitoneal injection of test doses of imipramine (10, 20 and 40 mg/kg) induced a dose-dependent antinociception in non-tolerant mice, both in the first and second phases of the formalin test. The combination of morphine (1 mg/kg) with imipramine (10 mg/kg) showed a potentiated response in the second phase of the test. Combination of a single dose of morphine (1.5 mg/kg) with lower doses of imipramine (2, 4 and 8 mg/kg) did not show potentiation. The antinociceptive response of either morphine or morphine plus imipramine was reduced by the opioid receptor antagonist naloxone (2 mg/ kg). In order to induce tolerance, mice were treated subcutaneously with morphine (50 mg/kg) once daily for 3 days. On day 4, the antinociceptive effect of test doses of morphine or imipramine were assessed. Tolerance to the responses of test doses of morphine (3, 6 and 9 mg/kg), but not imipramine (10, 20 and 40 mg/kg) in both phases of the test was observed. Administration of lower dose of imipramine (4 mg/kg) before the test doses of morphine (3, 6 and 9 mg/kg) was not able to alter the expression of morphine tolerance. When imipramine was used during development of tolerance, either on days 1 and 2 or on days 2 and 3, the morphine tolerance in the second phase of the test was reduced. It is concluded that opioid receptor mechanism(s) may mediate the antidepressant-induced antinociception, however, imipramine may be useful in inhibiting morphine tolerance.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"87 3","pages":"131-7"},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21894086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4