Additive and synergistic inhibition of mammalian microsomal enzyme functions by piperonyl butoxide,safrole and other methylenedioxyphenyl derivatives

Zusammenfassung Piperonylbutoxyd, Methylendioxylanilin, Methyleugenol, Safranol und Vanillylamin bewirken eine additive Hemmung der Funktion mikrosomaler Enzyme in Mäusen, wenn sie zusammen in Dosen verabreicht werden, die einzeln inaktiv sind. Piperonylbutoxyd und Safranol induzieren synergistisch die Hemmung von Aminopyrenedemethylase-Aktivität. Es erfolgte keine synergistische Hemmung nach kombinierter Behandlung mit Pib. und hohen Dosen der strukturell verwandten, aber inaktiven Piperonylsäure.

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Supported by N.I.H. Grants No. C-6516 and No. Fr-05526.

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We thank Mrs.M. Sengupta and Mr.E. Greene for their technical assistance.     

Effect of carbobenzoxy,phenylacetyl and phenylpropionyl derivatives of amino acids on mammalian and bacterial asparaginase

Zusammenfassung Während Acylderivate von Aminosäuren mit mehr als einer aromatischen Gruppe (wie z.B. N-Phenylacetyl-S-benzyl-l-cystein) auf Rattenleberasparaginase eine stark hemmende Wirkung ausüben, werden Asparaginase ausEscherichia coli undErwinia cartovora durch solche Verbindungen nicht gehemmt.     

Comparison of the inhibition of avian and mammalian bone alkaline phosphatases by levamisole and compound R8231

Summary Alkaline phosphatases from mammalian bone are inhibited much more than chick bone alkaline phosphatase by levamisole and compound R8231. Doses of R8231 (10^–4 to 10^–5 M) that almost completely inhibit mammalian alkaline phosphatases do not inhibit the growth of embryonic rat femurs in vitro. R8231 should be an excellent biological probe for the function of alkaline phosphatase in bone metabolism.Acknowledgments. This work has been supported by funds from the Medical Research Council.     

Cystamine inhibition of enzyme induction and acetate oxidation inPseudomonas aeruginosa and reversal by high salt concentrations

Riassunto L'inibizione della ossidazione di acetato e della induzione di benzoato-ossidasi da parte della cistamina in un ceppo diPseudomonas aeruginosa, varia colla concentrazione del mezzo nel quale le cellule sono sospese. L'effetto inhibitorio diminuisce con l'aumentare della concentrazione del buffer. Altre diamine e cistamina in forma ridotta sono inattive. La cistenia inibisce le medesime reazioni ma il suo effetto è indipendente della concentrazione del mezzo di sospensione. La cistina è priva di effetto.     

Effect of platinum derivatives on the inducible and repressible liver microsomal enzyme systems in the rat: inhibition of zoxazolamine-hydroxylase and induction of dimethyl-nitrosamine demethylase isoenzymes by cis-dichlorodiamine platinum (cis-PtCl2(NH3)2) and ammonium hexachloroplatinum (PtC16(NH4)2)]

Two platinum derivatives, cis-PtCl2(NH3)2 and PtCl6(NH4)2 have been studied for their effects on the Rat on cytochrome P450 in hepatic parenchyma on zoxazolamine-hydroxylase, a typical inducible system and on the two isoenzymes of dimethyl-nitrosamine demethylase, typical repressible systems. The inhibitory effect of PtCl6(NH4)2 on zoxazolamine-hydroxylase activity, previously shown by the authors, has been confirmed. The cis-PtCl2(NH3)2 also significantly inhibits zoxazolamine-hydroxylase activity. On the other hand, both of the platinum derivatives decrease cytochrome P450 level and enhance the dimethyl-nitrosamine metabolism. These various effects and their relationship are discussed.     

Comparative study of the sensitivity of acetylcholinesterases and cholinesterases from animal and bacterial sources to inhibition by serotonin and its derivatives

Summary Serotonin was found to inhibit human erythrocyte and electric-eel acetylcholinesterase activities. The serotonin amino group, free of negative charges in its vicinity and its hydroxyl group, were important for the inhibition. Serotonin precursors and several related compounds had little or no effect. Human plasma cholinesterase was also inhibited by serotonin and tryptamine. In contrast to these animal enzymes, the cholinesterase ofPseudomonas aeruginosa was refractory to serotonin and its derivatives under the same experimental conditions.     

Comparative study of the sensitivity of acetylcholinesterases and cholinesterases from animal and bacterial sources to inhibition by serotonin and its derivatives.

Serotonin was found to inhibit human erythrocyte and electric-eel acetylcholinesterase activities. The serotonin amino group, free of negative charges in its vicinity and its hydroxyl group, were important for the inhibition. Serotonin precursors and several related compounds had little or no effect. Human plasma cholinesterase was also inhibited by serotonin and tryptamine. In contrast to these animal enzymes, the cholinesterase of Pseudomonas aeruginosa was refractory to serotonin and its derivatives under the same experimental conditions.     

Inhibition of lymphocyte blastogenesis by diazepam, meprobamate, and other psychotropic drugs]

Imipramine, diazepam, chlordiazepoxide, and meprobamate inhibit incorporation of 3H-thymidine in human lymphocytes in culture. For the first three drugs, 50% inhibition occurs at a concentration of 5 X 10(-5) M, and for meprobamate at a concentration of 10(-3 M. Ethanol has no action up to 10(-1) M.     

Thyroxine administration and the uptake of amino acids by liver cell nucleolus,nucleus and cytoplasm,and by other cell types

Résumé L'administration de thyroxine cause une chute de l'incorporation de la phénylalanine-H³ et du tryptophane-H³ par divers organes, excepté le foie. Le cytoplasme et les noyaux des hépatocytes ont presenté une plus grande concentration de substance injectée.

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This investigation was supported by grants from Fundaçao de Amparo à Pesquisa do Estado de São Paulo, Rockefeller Foundation, and Conselho Nacional de Pesquisas.

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The help of Profs.L. C. U. Junqueira andC. P. Leblond as well as the technical assistance of MissE. Freymüller are acknowledged.     

Glycogenolytic effect and inhibition of glycogen phosphorolysis by 1, 2, 4-dinitrophenol in skeletal muscle

Resumen La fosforilaseb del músculo esquelético es inhibida por el 2,4-dinitrofenol, de acuerdo con nuestras observaciones anteriores. La fosforilasea no es inhibida por la droga.     

The effect of intoxication induced in rat liver by carbon tetrachloride,ethionine and white phosphorus on the level of microsomal cytochromesb 5 and P−450

Riassunto L'intossicazine di ratti Wistar con tetracloruro di carbonio (CCl₄) causa nel fegato una marcata diminuzione dei citocromi microsomialib ₅ e P_–450. L'etionina e il fosforo bianco, somministrati anch'essi ad una dose capace di determinare degenerazione grassa del fegato, non influenzano significativamente il livello dei due citocromi microsomiali.     

Depression of experimental gastric ulcers and acute pancreatitis in rats treated by 5-azacytosine, 5-azacytidine and their N-methyl derivatives

5-Azacytosine, 1-methyl-5-azacytosine and 5-azacytidine administered to rats with a ligated pylorus block gastric secretion, gastric acidity, the extent of hemorrhage and the number and size of gastric defects. The same drugs also depress the development of experimental acute pancreatitis mediated in rats by interstitial administration of 7.5% natrium cholate into the pancreas in vivo. The drugs affected the amount of abdominal fluid and 6 h after the treatment the pathological changes were significantly decreased.     

Depression of experimental gastric ulcers and acute pancreatitis in rats treated by 5-azacytosine, 5-azacytidine and their N-methyl derivatives

Summary 5-Azacytosine, 1-methyl-5-azacytosine and 5-azacytidine administered to rats with a ligated pylorus block gastric secretion, gastric acidity, the extent of hemorrhage and the number and size of gastric defects. The same drugs also depress the development of experimental acute pancreatitis mediated in rats by interstitial administration of 7.5% natrium cholate into the pancreas in vivo. The drugs affected the amount of abdominal fluid and 6 h after the treatment the pathological changes were significantly decreased.