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11.
Rogosch T Sinning C Podlewski A Watzer B Schlosburg J Lichtman AH Cascio MG Bisogno T Di Marzo V Nüsing R Imming P 《Bioorganic & medicinal chemistry》2012,20(1):101-107
Dipyrone is a common antipyretic drug and the most popular non-opioid analgesic in many countries. In spite of its long and widespread use, molecular details of its fate in the body are not fully known. We administered dipyrone orally to mice. Two unknown metabolites were found, viz. the arachidonoyl amides of the known major dipyrone metabolites, 4-methylaminoantipyrine (2) and 4-aminoantipyrine (3). They were identified by ESI-LC-MS/MS after extraction from the CNS, and comparison with reference substances prepared synthetically. The arachidonoyl amides were positively tested for cannabis receptor binding (CB(1) and CB(2)) and cyclooxygenase inhibition (COX-1 and COX-2 in tissues and as isolated enzymes), suggesting that the endogenous cannabinoid system may play a role in the effects of dipyrone against pain. 相似文献
12.
Bhaskarrao Chinthapalli Chitra Raghavan O. Bläsing P. Westhoff A.S. Raghavendra 《Photosynthetica》2001,38(3):415-419
Phosphoenolpyruvate carboxylase (PEPC) was purified from leaves of four species of Alternanthera differing in their photosynthetic carbon metabolism: Alternanthera sessilis (C3), A. pungens (C4), A. ficoides and A. tenella (C3-C4 intermediates or C3-C4). The activity and properties of PEPC were examined at limiting (0.05 mM) or saturating (10 mM) bicarbonate concentrations.
The Vmax as well as Km values (for Mg2+ or PEP) of PEPC from A. ficoides and A. tenella (C3-C4 intermediates) were in between those of C3 (A. sessilis) and C4 species (A. pungens). Similarly, the sensitivity of PEPC to malate (an inhibitor) or G-6-P (an activator) of A. ficoides and A. tenella (C3-C4) was also of intermediate status between those of C3 and C4 species of A. sessilis and A. pungens, respectively. In all the four species, the maximal activity (Vmax), affinity for PEP (Km), and the sensitivity to malate (KI) or G-6-P (KA) of PEPC were higher at 10 mM bicarbonate than at 0.05 mM bicarbonate. Again, the sensitivity to bicarbonate of PEPC from
C3-C4 intermediates was in between those of C3- and C4-species. Thus the characteristics of PEPC of C3-C4 intermediate species of Alternanthera are intermediate between C3- and C4-type, in both their kinetic and regulatory properties. Bicarbonate could be an important modulator of PEPC, particularly
in C4 plants.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
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Cyclooxygenase-2-dependent bronchoconstriction in perfused rat lungs exposed to endotoxin. 总被引:3,自引:0,他引:3
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S. Uhlig R. N¼sing A. von Bethmann R. L. Featherstone T. Klein F. Brasch K. M. M¼ller V. Ullrich A. Wendel 《Molecular medicine (Cambridge, Mass.)》1996,2(3):373-383
BACKGROUND: Lipopolysaccharides (LPS), widely used to study the mechanisms of gram-negative sepsis, increase airway resistance by constriction of terminal bronchioles. The role of the cyclooxygenase (COX) isoenzymes and their prostanoid metabolites in this process was studied. MATERIALS AND METHODS: Pulmonary resistance, the release of thromboxane (TX) and the expression of COX-2 mRNA were measured in isolated blood-free perfused rat lungs exposed to LPS. RESULTS: LPS induced the release of TX and caused increased airway resistance after about 30 min. Both TX formation and LPS-induced bronchoconstriction were prevented by treatment with the unspecific COX inhibitor acetyl salicylic acid, the specific COX-2 inhibitor CGP-28238, dexamethasone, actinomycin D, or cycloheximide. LPS-induced bronchoconstriction was also inhibited by the TX receptor antagonist BM-13177. The TX-mimetic compound, U-46619, increased airway resistance predominantly by constricting terminal bronchioles. COX-2-specific mRNA in lung tissue was elevated after LPS exposure, and this increase was attenuated by addition of dexamethasone or of actinomycin D. In contrast to LPS, platelet-activating factor (PAF) induced immediate TX release and bronchoconstriction that was prevented by acetyl salicylic acid, but not by CGP-28238. CONCLUSIONS: LPS elicits the following biochemical and functional changes in rat lungs: (i) induction of COX-2; (ii) formation of prostaglandins and TX; (iii) activation of the TX receptor on airway smooth muscle cells; (iv) constriction of terminal bronchioles; and (v) increased airway resistance. In contrast to LPS, the PAF-induced TX release is likely to depend on COX-1. 相似文献
17.
Rainer Dü sing Frederic C. Bartter John R. Gill Jr. Hans-G. Gü llner Charles R. Lake Jr. 《Prostaglandins & other lipid mediators》1980,20(6):971-979
The role of prostaglandins (PG) in the effects of potassium (K+)depletion was studied in six normal women. A mean K+-deficit of 220 mEq was induced with and without concomitant treatment with indomethacin (150 mg/day). Mean serum K+ concentration decreased from 4.2 ± (S.E.) 0.1 to 3.2 ± 0.1 mEq/L without indomethacin and from 4.1 ± 0.1 to 3.2 ± 0.1 mEq/L with indomethacin. “Supine” and “upright” plasma renin activity (PRA) and plasma norepinephrine concentration (NE) were unaltered by K+ -depletion alone but decreased with indomethacin. Plasma aldosterone (PA) was suppressed during K+-depletion (control: 7.2 ± 2.6 ng/dl supine, 19.3 ± 8.1 ng/dl upright; K+-depletion: 2.6 ± 0.3 ng/dl supine, 5.5 ± 1.3 ng/dl upright) and was paralleled by a decrease in urinary aldosterone. K+-depletion decreased urinary PGE2 from 667 ± 133 to 343 ± 60 ng/day (P < 0.025) without a change in PGF2. The dose of exogenous angiotensin II (A II) which increased diastolic blood pressure by 20 mm Hg (pressor dose) was 7.1 ± 1.4 ng/kg/min during control and increased to 11.0 ± 0.7 ng/kg/min during K+-depletion (P < 0.05). Indomethacin increased the sensitivity to A II both during control (pressor dose: 4.9 ± 0.6 ng/kg/min) and K+- depletion (pressor dose: 6.0 ± 1.0 ng/kg/min). These results indicate that in healthy subjects, moderate short-term K+-depletion does not affect PRA or NE but decreases production of aldosterone and PGE2 by the kidney. The changes in vascular sensitivity to exogenous A II during K+-depletion and indomethacin and the decreases in plasma NE and PRA during indomethacin may be explained by changes in vascular vasodilator PG. 相似文献
18.
The square-planar bis chelate complexes Ni(R-sal)2 (= bis(N-alkyl)salicylaldiminato)nickel(II)) with R = (CH2)2Ph (I; Ph = phenyl), (CH2)3Ph (II), (CH2)4Ph (III) and (CH2)2(4-hydroxyphenyl) (IV) were prepared and characterized. ComplexesII and III meet the steric requirements for intramolecular aromatic ring stacking. Stopped-flow spectrophotometry was used to study the kinetics of ligand substitution in complexesI–IV by H2salen (=N,N′-disalicylidene-ethylenediamine) in acetone. For the substitution of the two bidentate ligands in Ni(R-sal)2 only one step is kinetically observed which follows a second-order rate law, rate =k[H2salen] [Ni(R-sal)2], with k = 43.4 (I), 64.0 (II), 87.0 (III) and 49.5 (IV) M−1 s−1 at 298 K. It is found, therefore, that the size of k does not change significantly upon lengthening of the alkane chain in Ni(Ph(CH2)nsal)2 from n = 2 to 4 and that there is no kinetic evidence for intramolecular stacking interactions. The equilibrium constants and thermodynamic parameters for the formation of the bis adductsIII·(py)2 and III·(MeOH)2 in acetone are reported. 相似文献
19.
A recently produced monoclonal antibody against human thromboxane synthase was used to purify the enzyme from platelets in a one-step procedure with good yields. The isolated protein exhibited a single band of about 58 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and contained one heme/mol. Although the visible spectrum of the oxidized enzyme displayed a peak at 418 nm like the previously isolated enzyme after dithionite reduction and CO addition, it shifted to 419 nm but not to 450 nm where only a small shoulder could be detected. Its catalytic activity was only 1-5% of the previous preparations, but with the same Km of about 10 microM and a ratio of thromboxane B2: 12-hydroxyheptadecatrienoic acid of 1:1. Studies with EPR spectrometry and inhibitors confirmed that only a minor part of the enzyme was in its native heme-thiolate conformation, whereas the major part had been converted to the inactive P420 form by the elution procedure. The amino acid analysis revealed 46% hydrophobic residues. According to the sequence of 26 amino acids from the N-terminus and two tryptic peptides no homology to one of the cytochrome P450 monooxygenases, or to cyclooxygenase, or to prostacyclin synthase was detected. 相似文献
20.
Gyöngyi Kenesi Hesham M. Shafik Attila W. Kovács Sándor Herodek Mátyás Présing 《Hydrobiologia》2009,623(1):191-202
The aim of this research was to test whether NH4
+ and NO3
− affect the growth, P demand, cell composition and N2 fixation of Cylindrospermopsis raciborskii under P limitation. Experiments were carried out in P-limited (200 μg l−1 PO4-P) chemostat cultures of C. raciborskii using an inflowing medium containing either 4,000 μg l−1 NH4-N, 4,000 μg l−1 NO3-N or no combined N. The results showed the cellular N:P and C:P ratios of C. raciborskii decreased towards the Redfield ratio with increasing dilution rate (D) due to the alleviation of P limitation. The cellular C:N and carotenoids:chlorophyll-a ratios also decreased with D, predominantly as a result of an increase in the chlorophyll-a and N content. The NH4
+ and NO3
− supply reduced the P maintenance cell quota of C. raciborskii. Consequently, the biomass yield of the N2-grown culture was significantly lower. The maximum specific growth rate of N2-grown culture was also the lowest observed. It is suggested that these differences in growth parameters were caused by the
P and energy requirement for heterocyte formation, nitrogenase synthesis and N2 fixation. N2 fixation was partially inhibited by NO3
− and completely inhibited by NH4
+. It was probably repressed through the high N content of cells at high dissolved N concentrations. These results indicate
that C. raciborskii is able to grow faster and maintain a higher biomass under P limitation where a sufficient supply of NH4
+ or NO3
− is maintained. Information gained about the species-specific nutrient and pigment stoichiometry of C. raciborskii could help to access the degree of nutrient limitation in water bodies.
Handling editor: Luigi Naselli-Flores 相似文献