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L-641,953 (R-8-fluoro-dibenzo[b, f]thiepin-3-carboxylic acid-5-oxide): a novel thromboxane-prostaglandin endoperoxide antagonist 总被引:1,自引:0,他引:1
R A Hall J R Rokach P Bélanger L Bianchi D Ethier A W Ford-Hutchinson Y Girard P Hamel R Hamel A Lord 《Canadian journal of physiology and pharmacology》1987,65(4):509-514
The effects of L-641,953 (R-8-fluoro-dibenzo[b, f]thiepin-3-carboxylic acid-5-oxide) have been studied on pulmonary and other smooth muscle preparations in vitro and in vivo. When studied in vitro on guinea-pig tracheal chains, L-641,933 produced significant shifts in the dose-response curves to the prostaglandin endoperoxide analogues, U-44069 (pA2 7.06) and U-46619 (pA2 7.14), and prostaglandin (PG) F2 alpha (pA2 6.33) had minimal activity against contractions induced by histamine (pA2 4.38), 5-hydroxytryptamine (pA2 4.63), and acetylcholine (pA2 4.56) and slightly enhanced relaxation induced by PGE2. When tested on the guinea-pig gall bladder strip in vitro, L-641,953 antagonized contractions induced by U-44069 (pA2 7.03) but was less active against those induced by PGF2 alpha (pA2 6.03), PGE1 (pA2 5.62), and histamine (pA2 4.84). When tested in vitro on the guinea-pig pulmonary artery, L-651-953 significantly antagonized contractions induced by U-44069 (pA2 7.04), U-46619 (pA2 7.14), and PGF2 alpha (pA2 7.16) but was less effective against contractions induced by histamine (pA2 4.19). Schild analysis indicated that L-641,953 was fully competitive against contractions of either the guinea-pig tracheal chain induced by U-46619 or the guinea-pig pulmonary artery induced by U-44069 and U-46619. When tested on human platelets in vitro L-641,953 inhibited aggregation induced by U-44069 (IC50 1.3 X 10(-6) M) but not ADP.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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T Antonelli M Morari A Magri C Bianchi 《Bollettino della Società italiana di biologia sperimentale》1991,67(10-11):965-971
The effects of different alpha-2 agonists on the spontaneous motility in naive and morphine tolerant mice were studied. Clonidine caused a reduction at the lower (1-3 micrograms Kg-1 i.p.) and higher (100 micrograms Kg-1 i.p.) doses and no effect at 10-30 micrograms Kg-1 i.p. in naive mice, while an increase was found at the intermediate doses (10-30 micrograms Kg-1 i.p.) in morphine tolerant mice. The clonidine-induced inhibition on spontaneous motility at the lower and higher doses was prevented both in naive and tolerant mice by idazoxan pretreatment. In morphine-treated animals the increase induced by clonidine was antagonized by prazosin. The action of guanabenz and guanfacine on locomotion differed from clonidine, by producing inhibition only at higher doses (100-300 micrograms Kg-1 i.p.). Clonidine, but not guanfacine or guanabenz, prevented the withdrawal syndrome precipitated by naloxone. Thus the only alpha-2 agonistic properties do not appear sufficient to explain the prevention of morphine abstinence by clonidine in mice, which can represent a single model to screen anti-withdrawal drugs. 相似文献
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Eugene M. Rinchik Terry Magnuson Bernadette Holdener-Kenny Gavin Kelsey Albert Bianchi Claudio J. Conti Fran?ois Chartier Kathryn A. Brown Stephen D. M. Brown Josephine Peters 《Mammalian genome》1992,3(Z1):S104-S120
Chair of Committee for Mouse Chromosome 7 相似文献
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Genetic analysis of blood pressure in the Milan hypertensive strain of rat (Rattus norvegicus) 总被引:1,自引:0,他引:1
Estimates of heritability (h2) of blood pressure level and the number of loci controlling the trait were derived from two genetic crosses involving the Milan hypertensive strain of rat and its control with normal blood pressure. In the genetic cross involving backcrosses, the estimates were h2 = 64% and the number of loci was two or three; there was some evidence of dominance of the alleles for normal blood pressures. In the other cross with only F2's, the degree of genetic determination (heritability in the broad sense) was 45%, involving at least three loci. 相似文献
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J Pohl-Rüling P Fischer D C Lloyd A A Edwards A T Natarajan G Obe K E Buckton N O Bianchi P P van Buul B C Das 《Mutation research》1986,173(4):267-272
Unstable chromosome aberrations induced by in vitro irradiation with zero plus seven low doses of 14.8 MeV D-T neutrons in the range 3.55-244 mGy have been analysed in human peripheral blood lymphocytes. In order to obtain the required large numbers of scored cells for such low doses, fourteen laboratories participated in the experiment. The dose responses for dicentrics, excess acentrics and total aberrations, fitted well to the Y = alpha D model. The alpha coefficient of yield for dicentrics, 1.60 +/- 0.07 X 10(-2) Gy-1, compares well with the values obtained in previous studies with D-T neutrons at somewhat higher doses. Results from a previous collaborative study using 250 kVp X-rays over a comparable dose range indicated the possible existence of a threshold below 50 mGy. In the present study there is no clear evidence for neutrons for such a threshold. However, the data were insufficient to permit the rejection of a possible threshold below approximately 10 mGy. 相似文献
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Effects of nitrilotriacetic acid on the induction of gene mutations and sister-chromatid exchanges by insoluble chromium compounds 总被引:2,自引:0,他引:2
P Venier A Montaldi C Gava L Zentilin G Tecchio V Bianchi S Paglialunga A G Levis 《Mutation research》1985,156(3):219-228
The influence of nitrilotriacetic acid trisodium salt (NTA) on the mutagenic and clastogenic activity of several water-insoluble or poorly soluble chromium compounds was determined by means of the Salmonella/microsome assay (plate test on TA100 strain) and the sister-chromatid exchange (SCE) test in mammalian cell cultures (CHO line). NTA in itself did not induce gene mutations nor did it increase the frequency of SCE. Cr(VI) compounds (Pb, Ba, Zn, Sr and Ca chromates) and an industrial Cr(VI) pigment, chromium orange (containing PbCrO4 PbO), were inactive or scarcely active mutagens in the Salmonella/microsome test when dissolved in water, but they were increasingly mutagenic when solubilized by 0.5 N NaOH or NTA (10 or 100 mg/ml). Also, the mutagenic activity of Cr(VI), contaminating an industrial Cr(III) pigment (chromite), was slightly enhanced by NTA. Mutagenicity of chromates was correlated with the amounts of Cr(VI) solubilized by NTA or alkali, as determined by the colorimetric reaction with diphenylcarbazide and atomic absorption spectrophotometry, and was decreased by incubation with microsomes, due to reduction of Cr(VI) to the genetically inactive Cr(III) form. In the SCE assay, the insoluble or poorly soluble Ba, Zn, Sr and Ca chromates and the insoluble Cr(VI) pigments zinc yellow (containing ZnCrO4 Zn(OH2], chromium yellow and molybdenum orange (both containing PbCrO4) were directly clastogenic due to cellular endocytosis taking place in prolonged treatments, and NTA significantly increased their chromosome-damaging activity. 相似文献
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