Inhibition sélective des «vraies» et «pseudo»-cholinestérases du rectus de grenouille

Summary The hydrolysis of acetylcholine chloride (0.01M) by frog's rectus extracts, is inhibited by low concentrations of 3318 CT (CI-50 3.2×10^–7) and high concentrations of D.F.P. (CI-50 1.3×10^–5). Inversely, the hydrolysis of butyrylcholine perchlorate is inhibited by low concentrations of D.F.P. (CI-50 3×10^–9) and high concentrations of 3318 CT (CI-50 3×10^–4). Both are inhibited by similar concentrations of neostigmine (CI-50 1.1×10^–7 and 1.5×10^–7). Frog's rectus thus contains true and pseudo-cholinesterases. The inhibitions produced by D.F.P. added to the muscle itself (and not the extract) correlates well with the potentiation of the corresponding ester. Sensitization to AcCh and to BuCh appears to be specifically related to the inhibition of Ac ChE for the former ester, of XChE for the second one.     

Inhibition and sex specific induction of spawning by serotonergic ligands in the zebra musselDreissena polymorpha (Pallas)

Serotonin (5-hydroxytryptamine, 5-HT) stimulates spawning in the zebra mussel (Dressena polymorpha), a macrofouling European bivalve that has recently invaded North America. To develop methods of controlling zebra mussel spawning, two vertebrate serotonin antagonists, methiothepin and metergoline, known to bind with high affinity to snail 5-HT receptors, were tested for their ability to block 5-HT-induced spawning in zebra mussels. Methiothepin inhibited 5-HT-induced spawning at concentrations as low as 10^–6 M. Metergoline (10^–4 M) inhibited 5-HT-induced spawning; however, at lower concentrations (10^–8 to 10^–5 M), metergoline by itself significantly induced spawning in male, but not female zebra mussels. Metergoline (10^–5 M)-induced male spawning was inhibited by 10^–5 M methiothepin. Thus, methiothepin is the most effective inhibitor and metergoline the most powerful inducer of spawning yet tested in zebra mussels.     

Effect of enkephalins in the presence of the antibiotic bacitracin in the longitudinal muscle strip preparation from guinea-pig ileum

Summary The antibiotic bacitracin (5×10^–5–4×10^–4 M) increases the inhibition of the contractile response caused by both enkephalin release and direct application of Met-enkephalin 5×10^–7 M in the longitudinal muscle strip preparation from guinea-pig ileum. This effect is attributed to an inhibition of enkephalin degrading peptidases by bacitracin.     

Phosphoramidon enhances allatostatin-mediated inhibition of juvenile hormone biosynthesis in the corpora allta of the cockroach,Diploptera punctata

Use of the enkephalinase inhibitor phosphoramidon in the in vitro radiochemical assay for juvenile hormone biosynthesis enhanced allatostatin-mediated inhibition of hormone production by corpora allata of the cockroach,Diploptera punctata. Significant increases in inhibition in day 2 virgin female CA by AST 1 (at 10^–7 M) and AST 4 (10^–8–10^–7 M) were observed in the presence of phosphoramidon (10^–5M or greater). No significant increases in inhibition were seen in CA from day 6 mated females with AST 4 (10^–9–10^–7M) and phosphoramidon combined. Phosphoramidon alone had no effect on JH biosynthesis. Analysis of allatostatin content of the CA, as determined by ELISA, revealed that addition of phosphoramidon to the medium increased the endogenous allatostatin conten in CA of virgin and mated females. The similarity in primary structure between allatostatins and enkephalin-like peptides and their similar distribution makes it probable that phosphoramidon acts by preventing breakdown of allatostatins within the CA.     

Effects of retinoic acid on embryonic development of mice in culture

Summary The effects of all-trans-retinoic acid (RA) (tretinoin) on the craniofacial development of mouse embryos were examined using whole embryo culture. In day 8 embryos cultured for 48 h, embryonic growth was inhibited concentration-dependently by all-trans-RA treatment. Most of the treated embryos exhibited hypoplasia of the primary palatal processes and a reduction in the development of the first viscreral arches. In day 10 embryos cultured for 48 h, although embryonic growth was not inhibited at any concentrations of all-trans-RA, median cleft lip (93%), hypoplasia of the primary palatal processes (37%) and limb reduction deformities (48%) occurred commonly. Furthermore, RA treatment greatly reduced the size of the secondary palatal processes. The incorporation of³H-thymidine in the treated maxillary processes was decreased to 65% of the control value at 1.0×10^–7 M alltrans-RA. These findings indicate that all-trans-RA is teratogenic in mouse whole embryo culture.     

The effect of perchlorate ion and some pharmacological agents on the sensitivity of the frog (Rana pipiens) rectus abdominis to acetylcholine

Zusammenfassung Die Reaktion des mit Eserin vorbehandelten musculus rectus abdominis des Frosches auf Acetylcholin liess sich durch Oxotremorin (2.0·10^–5 M), Arecolin (2.0·10^–5M), Aceclidin (1.0·10^–4 M) und Carbachol (2.0·10^–7 M) verstärken, während Atropin (1.0·10^–5 M) hemmend wirkte. Perchlorationen in Konzentrationen über 2 · 10^–4 M sensibilisierten den Froschmuskel erheblich und reduzierten die Grenzdosis, bei der eine Potenzierung durch Substanzen mit muskarinähnlicher Wirkung beobachtet wird. Alle beschriebenen Reaktionen liessen sich durch Gehirnextrakte verstärken, in denen zuvor Acetylcholin durch Kochen in alkalischer Lösung zerstört worden war.

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This work was supported by NIH Grants No. NB 03007 and No. 5-F1-GM-22,905.     

Naringenin inhibition on expiants in vitro ofCichorium intybus (Chicory)

Riassunto La naringenina alla concentrazione di 10^–4 M inibisce in modo totale l'emissione di gemme in radici diCichorium intybus in vitro senza tuttavia bloccare completamente la callogenesi. A concentrazioni scalari minori (10^–5, 10^–6, 10^–7 M) questa sostanza causa una inibizione solo nella fase iniziale dell'esperienza.     

Growth ofNostoc muscorum mutants in the presence of diuron (DCMU) and L-methionine-DL-sulfoximine

Summary Diuron (DCMU) is inhibitory to the photoautotrophic and photoheterotrophic growth of the N₂-fixing blue-green algaNostoc muscorum at concentrations of 1.0×10^–5 M and 2.0×10^–5 M, respectively. A mutant of this organism resistant to 5.0×10^–5 M DCMU under its photoheterotrophic growth conditions, with the ability to utilize DCMU as a carbon and nitrogen source for growth, and complete inability to grow photoautotrophically has been isolated. With the apparent defect in its photosynthetic ability, it is suggested that theDCMU ^r mutant lacks the step inhibited by 1.0×10^–5 M DCMU, and metabolizes DCMU by an existing enzyme system in the absence of such inhibition. That this enzyme may be glutamine synthetase (GS) is explained with the help of a L-methionine-DL-sulfoximine (MSO)-resistant mutant ofN. muscorum which is able to grow faster with 2.0×10^–5 DCMU and is known to contain an altered GS.Thanks are due to the Council of Scientific and Industrial Research, CSIR Complex, Govt. of India, New Delhi-110012, for appointing the author to the Scientists' Pool for undertaking researches on the physiological and genetic controls of nitrogen metabolism in blue-green algae, a part of which is presented in this literature.     

VIP and histamine H2 receptor activity in human fetal gastric glands

Summary Vasoactive intestinal peptide (VIP, EC₅₀=6.4×10^–10 M) and histamine (EC₅₀=3×10^–6 M) activated the cyclic AMP generating system in gastric glands isolated from two human fetuses at 23 weeks gestation. Histamine antagonism by the H₂ receptor blockers cimetidine (Ki=0.35×10^–6 M) and ranitidine (ki=0.51×10^–7 M) clearly characterized the histaminic activation as being of the H₂ type. It is suggested that these two vasoactive hormones may operate as neurocrine/paracrine regulators of the differentiation and/or function of the human gastric mucosa in utero.     

Effects of ouabain and furosemide on saliva secretion induced by sympathomimetic agents in isolated,perfused rat submandibular glands

Summary The presence of 10^–3 M ouabain or furosemide in the perfusate inhibited saliva secretion induced by either isoproterenol (10^–5 M) or phenylephrine (10^–5 M) from isolated rat submandibular glands and caused characteristic alterations in the electrolyte composition of saliva.     

Fatty acid modulation of antiestrogen action and antiestrogen-binding protein in cultured lymphoid cells

Summary Nonsteroidal antiestrogens reversibly and specifically inhibited the proliferation of two estrogen receptornegative lymphoid cell lines (EL4 and Raji) in a dose-dependent manner. [³H]Thymidine incorporation of concanavalin A-stimulated primary splenocytes was also inhibited by 10^–6 M clomiphene (1-[4-(2-diethylaminoethoxy)phenyl]-1,2-diphenyl-2-chloroethylene). The antiproliferative effect could be prevented by the simultaneous presence in the growth medium of 10^–5 M linoleic acid or 10^–5 M arachidonic acid but not by 10^–6 M estradiol. Both lymphoid cell lines had high affinity antiestrogen-binding sites whose affinity could be altered by conditions of growth. Growth of EL4 cells in RPMI 1640 medium supplemented with charcoal-pretreated 5% fetal calf serum (charcoal-stripped medium) resulted in significantly higher affinity (K_d 0.54 nM±0.11 nM; n=6) than growth in medium supplemented with untreated serum (complete medium) (K_d=1.68 nM±0.48 nM; n=6) (p<0.001). This change in affinity was partly due to removal of fatty acids from the growth medium by charcoal pretreatment, since addition of 10^–5 M linoleic acid or 10^–5 M gamma-linolenic to charcoal-stripped medium decreased the affinity of the antiestrogen-binding protein. In contrast, growth in 10^–5 M stearic acid or 10^–5 M oleic acid did not significantly alter the affinity of the antiestrogen-binding protein, whereas 10^–5 M palmitic acid significantly increased its affinity. The same fatty acids were also tested for their intrinsic effects on EL4 cell proliferation. Oleic, linoleic and gamma-linolenic acids were growth stimulatory while stearic and palmitic acids were not. Thus linoleic and gamma-linolenic acids whose presence in the growth medium was associated with decreased affinity of [³H]tamoxifen (1-[4-(2-dimethylaminoethoxy)phenyl]-1,2-diphenylbut-1(Z)-ene) binding to the intracellular antiestrogen-binding protein were also growth stimulatory. Unsaturated fatty acids have previously been shown to inhibit binding of [³H]tamoxifen to the antiestrogen-binding protein in a cell-free system. The present observations demonstrate that unsaturated fatty acids also modify the affinity of the antiestrogen-binding protein in intact cells.     

Influence of cyclic nucleotides on protein synthesis in vascular smooth muscle

Summary The incorporation of leucice-¹⁴C into protein in bovine mesenteric arteries was augmented by cyclic GMP (10^–3 M) and decreased by cyclic AMP (10^–3 M). There was no effect of 5 AMP (10^–3 M). The phosphodiesterase inhibiting drugs theophylline (10^–3 M) and papaverine (5×10^–5 g/ml) both decreased the leucine-¹⁴C incorporation.We are indebted to Mrs.Lena Burlin for hear assistance. Finacial support has been provided by the Swedish State Medical Research Council (No. 04X-101X-4498).     

Drug interactions in intestinal absorption of3H-digitoxin in rats

Summary The absorption of³H-digitoxin from perfused rat small intestine was inhibited by probenecid (1.0×10^–2 M), ethacrynic acid (0.5×10^–3 M), and mersalyl (8.0×10^–3 M) indicating that digitoxin absorption is at least partly an active process.     

Die Wirkung von Theophyllin auf den cellulären Ca-Stoffwechsel des Warmblüterherzens

Summary In isolated, electrically driven, left guineapig atria, theophylline (5×10^–4 g/ml) increased the rate of⁴⁵Ca uptake and release without affecting the total myocardial Ca content and the amount of exchangeable cellular Ca. In sheep and calf heart preparations, theophylline (10^–4–10^–3 g/ml) increased Ca inward current during excitation (as examined indirectly by Ca dependent changes of membrane potential in TTX-containing solutions) as well as tension development. It is concluded that the positive inotropic effect of theophylline in mammalian hearts is due to an increase in Ca influx during the excitation process.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Hemmung der durch Proteuslipopolysaccharide gesteigerten Leukozytenemigration in vitro durch antiinflammatorische Corticosteroide

Summary The migration of leucocytes from the buffy coat of chicken blood is slightly but irregulatly inhibited by cortison. If migration of leucocytes is increased by proteus lipopolysaccharide, cortison in concentrations of 10^–4–10^–6, and other anti-inflammatory steroids, produce a pronounced and constant inhibition of leucocytic migration.     

Influence of atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) on auxin metabolism of plants

Zusammenfassung Die Enzymaktivität der IES-peroxidase in Hafer-Koleoptilen wurde durch Atrazin in Konzentrationen von 10^–10–10^–21 M gehemmt, im Konzentrationsbereich von 10^–6–10^–8 M gesteigert. Atrazin förderte ferner das Wachstum von Sojabohnen-Kallusgewebe in Gegenwart von 5 mg/l Kinetin und 10^–10 bis 10^–18 M Atrazin im Nähragar. Diese Einwirkung von Atrazin auf den Wuchsstoffmetabolismus der Pflanzen gibt erste Anhaltspunkte, die zahlreich beobachteten Förderungen bzw. Hemmungen des Pflanzenwachstums unter dem Einfluss von Atrazin zu erklären. Die Resultate bilden weiterhin eine neue Grundlage für eine mögliche Interpretation des «Proteineffekts» der Triazine.     

Zum Nachweis von Aminen im 10−10-Mol-Maßstab. Trennung von 1-Dimethylamino-naphthalin-5-sulfonsäure-amiden auf Dünnschichtchromatogrammen

Summary For the sensitive determination of amines their 1-dimethyl-amino-naphthalene-5-sulphonyl derivatives were separated in two-dimensional thin-layer chromatograms. 10^–10–10^–11 mole per amine can be detected, when the fluorescence of the DANSyl-compounds is excited by the 365 mµ Hg line.     

Age and evolution of bacteria

Summary Age and evolution of bacteria can be estimated, including facts and hypotheses belonging to morphology, biochemistry, paleontology, ecology and pathogenicity. The corresponding dates are summarized in the following.About 3.5×10⁹ years: Origin of heterotrophic eobiontes.—About 3.0×10⁹ years: The increasing lack of prebiogenic substances is due to the evolution of the respiratory pathway, that is due to the evolution of the photoautotrophy and now released O₂ is due to the evolution of strictly aerobic cells. There is, simultaneously, a transition of spheres to long forms, development of an amoebalike motility, the evolution of spirochetes and the substitution of cholesterol for cardiolipin in the more evolved cells (i.e. strictly aerobic cells etc.).—About 2.0×1.0×10⁹ years: Evolution of the eucyte by symbiosis of a great, primitive, anaerobic, cholesterol-containing cell with a little, strictly aerobic, cardiolipin-containing cell, with a spirochete and in some extent also with photoautotrophic cell.—About 1.0×10⁹ years (maximum: 1.8–1.5×10⁹ years, minimum: 7×10⁸ years): Evolution of metazoa and begin of cell differentiation.—About 2.0–1.0×10⁹ years: Evolution of the bacterial murein sacculus and then development of flagella mediated motility.—About 6×10⁸ years (maximum:1.0×10⁹ years, minimum: 4.5×10⁸ years): Evolution of the gram-negative cell wall.—About 4.0×10⁸ years: Evolution of the gram-positive cell wall.—About 5.0×10⁸ years: Gram-negative, strictly anaerobic bacteria become the first enteric bacteria in coelenterates. About 4.0×10⁸ years: gram-negative, microaerophilic bacteria become Enterobacteriaceae in vertebrates in addition to the strictly anaerobic organisms.—About 3.0–2.0×10⁸ years: Consolidation of the Salmonella in reptiles.—About 2.0–1.5×10⁸ years: Consolidation of Escherichia and other coliform species in mammals.—About 10⁶ years: Evolution of typically human pathogenic organisms, transmitted in homogeneous-homonomous infection ways, i.e. N. gonorrhoeae, S. typhi, T. pallidum, etc.Dedicated to Prof. H. Habs, Bonn, to his 75th anniversary on 11 September 1977.Acknowledgment. I thank Prof. F. Müller, Hamburg, and Prof. P. Sitte, Freiburg i. Br., for stimulating discussions.     

Effects of cycloheximide on protein synthesis in human lung tumors,regenerating rat liver and hepatomas

Summary 10^–4 M cycloheximide (CHM) inhibits leucine incorporation to about the same degree in slices of human lung tumors, rat hepatomas, regenerating livers and normal tissues. At 10^–6 M, CHM has a more pronounced effect on tumor tissue and regenerating liver than on normal tissues. 10^–8 M CHM stimulates protein synthesis in normal rat liver slices.     

The uptake of iodinated protein by spleen cells of guinea-pigs in vitro

Zusammenfassung 6×10^–10 g bis 10^–4 g J 125 Rinderserum-Albumin (BSA) bzw. 1,0×10^–7 bis 1,0×10^–6 g J 125 Rinderserum--Globulin (BGG) werden 3 × 10⁷ Milzzellen normaler Meerschweinchen in vitro angeboten. Unabhängig von der Höhe des Angebotes beträgt die Menge des aufgenommenen BSA 1%, die des aufgenommenen BGG 10% des Angebotes. Durch 4C Inkubations-temperatur wird die Aufnahme z.T. behindert. Die Aufnahme findet nach wenigen Sekunden Inkubationszeit statt und ist nach etwa 2–3 min abgeschlossen.

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The work was supported by a grant of the Stiftung Volkswagenwerk and of the Deutsche Forschungsgemeinschaft.