α-andβ-activity of O-methylated derivatives of norepinephrine and epinephrine

Summary Metanephrine, iso-metanephrine, normetanephrine and isonormetanephrine were tested for - and -activity on various tissues obtained from rats, guinea-pigs and cats. It was found that methylation of the hydroxyl groups of norepinephrine or epinephrine in either the 3-or 4-position markedly reduces or abolishes -and -activity with the exception of the nictitating membrane of the cat. This receptor seems to show a tissue difference.Acknowledgment. W. H. V. would like to thank the Federal Republik of Germany for the U. S. Senior Scientist Award which enabled him to work at the Department of Pharmacology, University of Mainz, and to conduct part of this work. W. H. V. would also like to thank Prof. Dr E. Muscholl, Mainz, for his hospitality, help and advice during this stay.     

On the mineralocorticoid and hypertensogenic properties of 16β-Hydroxy-Dehydroepiandrosterone

Summary Dosages of either 1 or 2 mg daily of 16-hydroxy-dehydroepiandrosterone, given to mononephretomized, salt-loaded female rats, had no detectable effect upon saline consumption, blood pressure, kallikrein excretion or heart and kidney weight. Its alleged mineralocorticoid properties, as judged by these criteria, were not demonstrable.This study was supported by a grant No. HL 15319 from the United States Public Health Service.     

Comparison of the effects of lithium,β-phenylethylamine and tyrosine onXenopus embryos

Résumé On a étudié les effets du lithium, de la -phényléthylamine et de la tyrosine sur le développement embryonnaire deXenopus laevis. La tyrosine n'a pas d'effet, mais le lithium ou la -phényléthylamine ont végétalisé les embryons s'ils ont été exposés avant le stade blastula.     

Levels ofβ-trace protein and lysozyme in human amniotic fluids

Summary The levels of -trace protein and lysozyme were estimated in amniotic fluids from normal fetuses and from fetuses with neuraltube defects. The values of these proteins in normal amniotic fluids were found to be similar to those detected in fetuses with anencephaly and spina bifida. The levels of lysozyme were shown to be correlated with gestational age.     

Antihypertensive and cardiac effects of two novelβ-adrenoceptor blocking drugs

Summary Two new-adrenoceptor blocking drugs with acute antihypertensive and positive inotropic effects are described: Compound A (2-[4-(3-tert. butylamino-2-hydroxypropoxy)phenyl]-4-trifluoromethylimidazole) and MK-761 (2-(3-tert. butylamino-2-hydroxypropoxy)-3-cyanopyridine hydrochloride). In SH rats both compounds, given orally, lowered arterial pressure and were more potent than hydralazine. The antihypertensive effect of compound A but not of MK-761 was antagonized by timolol. Both compounds had positive inotropic activity on cat heart papillary muscles; these effects were antagonized by timolol. The pretreatment of animals with reserpine greatly reduced the positive inotropic effect of MK-761 but not of compound A. The acute antihypertensive and positive inotropic effects of compound A are likely to be at least partially due to stimulation of-adrenoceptors, e.g. intrinsic sympathomimetic activity. The effects of MK-761 on the same parameters appear to be mediated by different mechanisms.     

Microbiological transformations ofβ-sitosterol and stigmasterol by a soil pseudomonad

Summary Fermentation of -sitosterol by a soil pseudomonad resulted in the formation of 4-stigmasten-3-one, 4-stigmasten-3-one-6-ol and 5-stigmasten-3, 7-diol. In case of stigmasterol the metabolites isolated and characterized were 4,22-stigmastadien-3-one, 4, 22-stigmastadien-3-one-6-ol and 5,22-stigmastadien-3, 7-diol.The soil pseudomonad strain (BS-305) is maintained at 4°C on nutrient-agar slants.     

Alterations ofβ-adrenoceptor-density and cAMP-synthesis in rat-erythrocytes after stress erythropoiesis

Summary During the maturation of red blood cells from rats after stress erythropoiesis, adenyl cyclase activity and -adrenoceptor density (pmoles/mg protein) decrease at distinctly different rates suggesting a different turnover of these membrane units.Acknowledgments. This work was supported by the Deutsche Forschungsgemeinschaft. The skillful technical assistance of Mrs I. Groth and Mrs C. Kiele is gratefully acknowledged. The liquid scintillation spectrometer was a gift from the Dr Robert-Pfleger-Stiftung.     

Kinetic studies on soluble and membrane-bound dopamineβ-hydroxylase isolated from storage vesicles of heart and adrenal medulla of different species

Summary IdenticalK _m-values for soluble and membrane-bound dopamine -hydroxylase isolated from adrenal medullary vesicles of different species were obtained; the same holds true for both forms of the enzyme of heart vesicles.The excellent technical assistance of MissSabine Klemt is gratefully acknowledged.     

α- andβ-Guttiferins

Zusammenfassung Die Isolierung, Charakterisierung und antibiotischen Eigenschaften von-Guttiferin (I), C₃₃H₃₈O₈ (Smp. 113–115°), aus den Samenhülsen und vom nahe verwandten-Guttiferin (II), C₂₉H₃₆O₆ oder C_33–34H_38–40O₈ (Smp. 86–91°) (möglicherweise identisch mit-Gambogasäure), aus Gummigutt, dem harzigen Sekret vonGarcinia morella, wurden beschrieben und ihre Verwandtschaft zu Morellin und Moreollin, den beiden bekannten Pigmenten der Samenhülsen, dargelegt. Für I wurde eine Partialstruktur vorgeschlagen. Die Bildung derselben komplexen bromhaltigen Säure vom Smp. 199 bis 200° unter der Einwirkung von Natriumhypobromit auf I und II spricht ferner für deren nahe strukturelle Verwandtschaft.     

The opposed influences ofβ-adrenergic stimulation and adenosine on the frequency-force relationship of isolated left atria of guinea-pigs

Summary The normal frequency-force relationship of left guinea-pig atria can be largely suspended when strong -adrenergic stimulation by orciprenaline is antagonized by the negative inotropic effect of adenosine, so that contraction amplitude is nearly equal at an intermediate level over a wide range of stimulation rates. Curves obtained with a new method for recording continuous frequency-force loops are presented.     

β-alanine and α-L-alanine inhibit the exploratory activity of spontaneously hypertensive rats

Summary 1% -alanine and -L-alanine, when given for 7 days as the only drinking fluid, inhibited the exploratory activity of adult male spontaneously-hypertensive rats (SHR)_but not that of the normotensive Wistar-Kyoto rats (WKR). -Alanine decreased the taurine level in the liver of both strains and in the platelets of SHR. -Alanine decreased the taurine level in the liver of WKR and in the platelets of SHR.This study was supported by the Sigrid Jusélius Foundation.     

Influence of cyproterone acetate on the activity ofβ-glucuronidase in the hypothalamus and cerebral cortex of the male mouse

Summary Daily s.c. injections of cyproterone acetate greatly decrease the protein content and-glucuronidase activity in the mouse hypothalamus. These effects are reversible and the recovery capacity of the animal seems to be inversely related to the duration of antiandrogenic treatment.Financial aid was given by CNR (finalized project Biologia della Riproduzione) and Ministry of Education. Thanks are also due to Prof. G. Chieffi for suggestions and to Mr R. Auriemma for maintenance of experimental animals.     

Circadian rhythm ofβ-glucuronidase

Summary The circadian rhythm of rat liver-glucuronidase has been studied in animals kept under highly standardized laboratory condition. A clear 24 h rhythm has been observed for this enzyme with a peak activity at 01.00 h and a trough at 13.00 h.The work was carried out in Institut für Anatomie I, Medical School, Hannover (Federal Republic of Germany). Supported by grants from Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 146 and VW Stiftung, Hannover A2 11.2000.     

Involvement of xanthine oxidase and hypoxia-inducible factor 1 in Toll-like receptor 7/8-mediated activation of caspase 1 and interleukin-1β

Inflammatory reactions to ssRNA viruses are induced by the endosomal Toll-like receptors (TLRs) 7 and 8. TLR7/8-mediated inflammatory reaction results in activation of the Nalp3 inflammasome via an unknown mechanism. Here we report for the first time that TLR7/8 mediate activation of xanthine oxidase (XOD) in an HIF-1α-dependent manner. XOD produces uric acid and reactive oxygen species, which could activate Nalp3 and therefore induce activation of caspase 1, known to convert inactive pro-IL-1β into active IL-1β. Specific inhibition of the XOD activity attenuates TLR7/8-mediated activation of caspase 1 and IL-1β release. These results were obtained using human THP-1 myeloid macrophages. The findings were verified by conducting in vivo experiments on mice.     

The binding of polyphenols (rutin and some of itsO-β-hydroxyethyl derivatives) to human serum proteins

Summary A binding of polyphenols (rutin and its o--hydroxyethyl derivatives) to human serum was demonstrated. The results showed an increase of binding proportional to the number of free phenolic groups on the molecule of rutin.Acknowledgments. We should like to thank MissC. Gaillard and MissE. Engels for their valuable assistance in this study.     

Role of Cys221 and Asn116 in the zinc-binding sites of the Aeromonas hydrophila metallo-β-lactamase

The CphA metallo--lactamase produced by Aeromonas hydrophila exhibits two zinc-binding sites. Maximum activity is obtained upon binding of one zinc ion, whereas binding of the second zinc ion results in a drastic decrease in the hydrolytic activity. In this study, we analyzed the role of Asn116 and Cys221, two residues of the active site. These residues were replaced by site-directed mutagenesis and the different mutants were characterized. The C221S and C221A mutants were seriously impaired in their ability to bind the first, catalytic zinc ion and were nearly completely inactive, indicating a major role for Cys221 in the binding of the catalytic metal ion. By contrast, the binding of the second zinc ion was only slightly affected, at least for the C221S mutant. Mutation of Asn116 did not lead to a drastic decrease in the hydrolytic activity, indicating that this residue does not play a key role in the catalytic mechanism. However, the substitution of Asn116 by a Cys or His residue resulted in an approximately fivefold increase in the affinity for the second, inhibitory zinc ion. Together, these data suggested that the first zinc ion is located in the binding site involving the Cys221 and that the second zinc ion binds in the binding site involving Asn116 and, presumably, His118 and His196.Received 3 March 2003; received after revision 4 August 2003; accepted 25 August 2003     

Action ofβ-(4-chlorophenyl-GABA) on uptake and metabolism of GABA in different subcellular fractions of rat brain

Summary -(4-chlorophenyl)-GABA, a GABA mimetic compound, acts as an inhibitor of GABA metabolism in both synaptosomal and extrasynaptosomal compartments. It has no significant action on GABA or Glu uptake by synaptosomes.     

Optical rotatory dispersion and spectral data of some steroidal ring D ketol acetates of the 14β-series

Zusammenfassung Die optische Rotationsdispersion sowie die UV- und IR-Spektren der Epimeren von 17-Acetoxy-16-keto-bzw. 16-Acetoxy-17-keto-14-steroiden wurden gemessen. Mögliche Beziehungen zwischen Rotationsdispersion und Stereochemie der untersuchten Verbindungen werden diskutiert.

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Paper LXI ofOptical Rotatory Dispersion Studies. For Paper LX seeC. Djerassi, Science134, 649 (1961).     

Characterization of 17β-estradiol 3-(β-D-glucopyranoside) and 17-(α-D-glucopyranoside) as the metabolites of 17β-estradiol in the cultured ovaries of the silkworm,Bombyx mori

Summary The structures of the metabolites formed upon incubation of 17-estradiol with the ovaries of silkworm,Bombyx mori, have been determined as 17-estradiol 3-(-D-glucopyranoside) (1) and 17-(-D-glucopyranoside) (2) by spectroscopic means.