Abstract:1. Previous studies have shown that the macrolide antibiotics, such as oleandomycin and erythromycin, enhance their own transformation into a stable metabolite-cytochrome P-450 complex, thus impairing monooxygenase activity. This cytochrome P-450 induced by macrolides is similar to the major form induced in rats by pregnenolone-16 alpha-carbonitrile (PCN) (III A1 isozyme). 2. The cytochrome P-450 isozyme induced in rats by PCN or macrolide antibiotics bound dihydroergotamine (DHE) with high affinity and was al… Show more
“…Although in terms of sensitivity, enzymatic and radioimmunological techniques, such as, e.g., EIA [17,23] and RIA [9,[17][18][19][20][21][22] provide excellent sensitivity with limits of quantitation spanning the range from the lower ng/ml to lower pg/ml level, they very often are lacking specificity. As a consequence, more or less marked cross-reactions have to be taken into account but nevertheless "group" determinations may be accomplished.…”
Section: Sample Preparation Chromatographic Separation and Detectionmentioning
confidence: 99%
“…The fact that ergot alkaloids possess different amine functions requires the use of buffered mobile phase systems and performed by either isocratic elution [6,8,14,[24][25][26][28][29][30] or in the gradient mode [1,[7][8][9]13,15,16,25] on C 18 and C 8 columns. In some applications acetonitrile-10 mM ammonium carbonate mixtures [1,9,13,24,25,28] were used but except Ref.…”
Section: Sample Preparation Chromatographic Separation and Detectionmentioning
confidence: 99%
“…Hitherto available data from structurally-related compounds imply involvement of the cytochrome P450 system in the oxidative pathway when passing the liver [1,9]. This family of oxidizing enzymes composes of several isoforms with different substrate specificities [10] and is mainly responsible for the metabolism of a vast number of drugs [11,12].…”
Section: Introductionmentioning
confidence: 99%
“…For this reason, either radioimmunological methods (radioimmunoassay, RIA) [9,[17][18][19][20][21][22] and enzyme immunoassays (EIA) [17,23] have been preferentially used in the past. However, liquid chromatographic procedures, coupled to mass spectroscopic detection (MSD), provide some crucial advantages, in particular with concern to specificity.…”
Section: Introductionmentioning
confidence: 99%
“…However, liquid chromatographic procedures, coupled to mass spectroscopic detection (MSD), provide some crucial advantages, in particular with concern to specificity. Indeed, high performance liquid chromatographic methods [1,[6][7][8][9]13,[15][16][17][24][25][26][27][28][29][30] prevail in analytical investigations of ergot alkaloids targeted either to get more precise insight into the metabolic pattern or to obtain thorough information of their concentrations in a biological environment, such as, e.g., serum or plasma, urine, tissue, etc. Among them three methods apply the selective "on-line" LC-MS hyphenation [13,15,17] allowing direct and unequivocal structural assignment of the compounds of interest even in those cases where co-elution of two or more species occurs provided ionization energy is not quantitatively consumed by the interfering ones.…”
“…Although in terms of sensitivity, enzymatic and radioimmunological techniques, such as, e.g., EIA [17,23] and RIA [9,[17][18][19][20][21][22] provide excellent sensitivity with limits of quantitation spanning the range from the lower ng/ml to lower pg/ml level, they very often are lacking specificity. As a consequence, more or less marked cross-reactions have to be taken into account but nevertheless "group" determinations may be accomplished.…”
Section: Sample Preparation Chromatographic Separation and Detectionmentioning
confidence: 99%
“…The fact that ergot alkaloids possess different amine functions requires the use of buffered mobile phase systems and performed by either isocratic elution [6,8,14,[24][25][26][28][29][30] or in the gradient mode [1,[7][8][9]13,15,16,25] on C 18 and C 8 columns. In some applications acetonitrile-10 mM ammonium carbonate mixtures [1,9,13,24,25,28] were used but except Ref.…”
Section: Sample Preparation Chromatographic Separation and Detectionmentioning
confidence: 99%
“…Hitherto available data from structurally-related compounds imply involvement of the cytochrome P450 system in the oxidative pathway when passing the liver [1,9]. This family of oxidizing enzymes composes of several isoforms with different substrate specificities [10] and is mainly responsible for the metabolism of a vast number of drugs [11,12].…”
Section: Introductionmentioning
confidence: 99%
“…For this reason, either radioimmunological methods (radioimmunoassay, RIA) [9,[17][18][19][20][21][22] and enzyme immunoassays (EIA) [17,23] have been preferentially used in the past. However, liquid chromatographic procedures, coupled to mass spectroscopic detection (MSD), provide some crucial advantages, in particular with concern to specificity.…”
Section: Introductionmentioning
confidence: 99%
“…However, liquid chromatographic procedures, coupled to mass spectroscopic detection (MSD), provide some crucial advantages, in particular with concern to specificity. Indeed, high performance liquid chromatographic methods [1,[6][7][8][9]13,[15][16][17][24][25][26][27][28][29][30] prevail in analytical investigations of ergot alkaloids targeted either to get more precise insight into the metabolic pattern or to obtain thorough information of their concentrations in a biological environment, such as, e.g., serum or plasma, urine, tissue, etc. Among them three methods apply the selective "on-line" LC-MS hyphenation [13,15,17] allowing direct and unequivocal structural assignment of the compounds of interest even in those cases where co-elution of two or more species occurs provided ionization energy is not quantitatively consumed by the interfering ones.…”
Nitric oxide (NO) is a well-documented effector molecule in rodent phagocytes but its synthesis in human neutrophils has been controversial. In this study, NO production in human neutrophils activated by chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) was measured in the presence of L-arginine (L-Arg) and N(G)-hydroxy-L-arginine (OH-L-Arg), the precursor and intermediate amino acids in NO synthesis, respectively. Incubation of fMLP-activated neutrophils with OH-L-Arg resulted in a production of nitrite, nitrate, and citrulline that was greater than with unstimulated neutrophils but was not inhibited by the NOS inhibitors L-NMMA and L-NIO or the cytochrome P450 inhibitor troleandomycin and was not seen when OH-L-Arg was replaced with L-Arg. This nitrite, nitrate, and citrulline production was not associated with any detectable NO synthesis because no increases in cyclic GMP were observed in the presence of phosphodiesterase inhibitors and in the presence or absence of superoxide dismutase. Moreover, no increases in the formation of the reaction product of NO with superoxide, peroxynitrite, were observed on addition of either OH-L-Arg or L-Arg to activated neutrophils, as assessed either by dihydrorhodamine oxidation or protein nitration. This suggests that, in spite of the production of nitrite, nitrate, and citrulline, commonly used indicators of NO formation, normal human blood neutrophils, are not producing detectable amounts of either NO or peroxynitrite when stimulated with fMLP in the presence of OH-L-Arg.
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