Zur Wirkungsweise einiger Katalase-Inhibitoren

Summary The mechanism of catalase inhibition by CN^–, N ₃ ^– , and SH^– has been investigated by a polarographic method. CN^– has been found to inhibit reversibly by a coordinating mechanism, whereas N ₃ ^– and SH^– inhibits catalase irreversibly.     

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.     

The molecular composition of a photographic fixing bath

Zusammenfassung In Thiosulfatlösungen von mäßiger Stärke bildet Silber die zwei Ionen Ag(S₂O₃) ₂ ^3– und Ag(S₂O₃) ₃ ^5– , deren Komplexkonstanten bestimmt wurden.     

Zur Stereochemie der Propandioldehydrase-Reaktion

Summary Propanedioldehydrase is shown to convert both (+)-(S)-2-²H-propanediol,3, and (–)-(R)-1-²H₂-propanediol,5, to specimens of deuterated propion-aldehyde, for which the (S)-configuration has been established. Thus, in the propanedioldehydrase reaction migration of hydrogen atoms from C–1 to C–2 always occurs with inversion of configuration.     

Selective killing of smooth muscle cells in culture by the ricin A-chain conjugated with monoclonal antibodies to a cell surface antigen via a dextran bridge

Summary Monoclonal antibodies to a surface antigen of the modulated smooth muscle cells originally isolated from the rat aorta media were conjugated with ricin A-chain via an oxidized dextran bridge. The interaction of cultured cells with the conjugates obtained and with control substances was monitored following incorporation of¹⁴C-leucine radioactivity. It was found that¹⁴C-leucine incorporation was suppressed by 80–90% at a conjugate concentration of 10^–6–10^–7 M. Antigen-negative cells (line IAR; rat hepatocytes) were insensitive to the conjugate at any concentration used. Control use of purified ricin A-chain, native or oxidized dextran, specific and nonspecific IgG did not affect normal¹⁴C-leucine incorporation. The data obtained may be useful for designing targeted drug transport systems and for selective screening of modulated smooth cells in vascular pathology models in vivo.     

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.     

Brain factor fromGalleria mellonella (Lepidoptera) stimulating silk gland activity

Brain extracts from day 1–4 last instar larvae ofGalleria mellonella (Lepidoptera) stimulate RNA synthesis in cultured silk glands from day 3 last instar larvae. When the fibroin-synthesizing posterior parts of silk glands were incubated for 3 h in vitro in the presence of brain extract (0.1 brain equivalent), [³H]-uridine incorporation into RNA was stimulated more than twofold. The stimulating effect of brain extract showed a dose response relationship. It is suggested that the heat-resistant and protease-sensitive brain factor is a peptide.     

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.     

Somatostatin inhibits in vitro release of luteinizing hormone releasing hormone from rat mediobasal hypothalamic slices

Summary Somatostatin, in concentrations ranging from 10^–10 M to 10^–7 M, induces a dose-dependent inhibition of LHRH release from mediobasal hypothalamic slices incubated in vitro. In contrast, VIP, secretin, glucagon, substance P, neurotensin and arginine-vasotocin do not affect spontaneous release of LHRH.     

Hemodynamic studies in a parabiotic model of portal hypertension

Summary Splanchnic and systemic hemodynamic studies were performed in a rat model of parabiosis and portal hypertension. A portal hypertensive and a normal rat were surgically united side to side. A hyperdynamic circulation, characterized by increased cardiac index (413±26 vs 318±23 ml·min^–1·kg^–1; p<0.05) and portal venous inflow (9.61±1.29 vs 6.33±0.36 ml·min^–1·100 g b.wt^–1; p<0.05), was found in all the portal hypertensive rats but not in the normal parabiotic partners. These results do not support the existence of a transferable humoral factor mediating the hyperdynamic circulatory state of chronic portal hypertension.Acknowledgment. The authors express their appreciation to Martha Shea for technical assistance.     

Kinetics and subcellular distribution of S35-taurine uptake in rat cerebral cortex slices

Zusammenfassung Die Kinetik der Aufnahme von S³⁵-Taurin in Rattencortex-Schnittchen wird im Konzentrationsbereich von 9×10^–8 M bis 5×10^–3 M untersucht. Nach Abzug des Transportes durch Diffusion (K _D ×S) findet man einen Mechanismus, der Michaelis-Menten Kinetik folgt (v _sat ), mitK _m =1,73×10^–4 M. Ein solcher Transport liegt nicht im Bereich des spezifischen «uptake» der Neurotransmitter. Auch die sehr niedrige Aufnahme-Rate und die subzelluläre Verteilung nach «uptake» sprechen gegen eine Neurotransmitter-Funktion von Taurin.     

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).     

Caclium causes the biphasic dose-response curve for pancreatic amylase secretion

Summary High concentrations of bethanechol (10^–4 to 10^–3 M) were effective stimulants of amylase secretion from the mouse pancreas if incubations are performed in low [ca²⁺] (0.1 mM) solutions but not if normal Krebs solution (2.56 mM Ca²⁺) was used. This inhibitory effect of Ca²⁺ at high secretagogue concentrations did not appear to be mediated through the microtubules or microfilaments.     

Temperaturabhängigkeit der elektrischen Leitfähigkeit einiger Tocopherole

Summary The electrical dark conductivity of several tocopherols has been measured and found to be analogous to that of organic semiconductors. Conductivity at 25°C varies between 10^–14 and 10^{–11 –1} cm^–1. The temperature dependence of the tocopherols yields a thermal activation energy of 1.6 ± 0.15 eV for most of the substances.     

Semisynthesis and biological properties of the [B24-leucine]-, [B25-leucine]- and [B24-leucine,B25-leucine]-analogues of human insulin

Summary Trypsin-catalyzed coupling of porcine desoctapeptide-insulin with synthetic octapeptides produced the [Leu^B24]-(I), [Leu^B25]- (II) and [Leu^B24, Leu^B25]- (III)analogues of human insulin. I, II and III displayed respectively 20–30%, 1–2% and 0.5% of the receptor binding activity of the normal hormone. Biological activities of these analogues seemed to be proportional to their binding potencies when assayed in vitro, while in an in vivo assay analogue I was fully active and II exhibited 10–20% of normal activity. III was less active than II in all assays tested.     

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.     

Kinetics and inotropic action of probenecid in guinea-pig heart in vitro

Summary Probenecid (100–750 g·ml^–1) was found to inhibit cardiac contraction force in untreated and digoxin-treated (100 g·ml^–1) isolated right guinea-pig atrium in vitro by a reversible process, without influencing beating frequency. At low concentrations (1.5–60 g·ml^–1),¹⁴C-probenecid was accumulated into right atrium by an oxygen-dependent process. Correlation between uptake and negative inotropic action of probenecid could not be found.     

Die Wirkung von Spirolactonen und von Herzglykosiden auf den Natrium- und Kaliumtransport an Erythrocyten

Summary Experiments made on human red cells showed that spirolactones (SC 5233 and SC 9420) added to the sample as dry powder (10^–3 g/ml) exert an inhibitory action on the active transport of sodium and potassium across the cell membrane. Spirolactone at its saturation concentration in serum (1.5×10^–5 g/ml), however, was ineffective.The inhibitory action was not affected by aldosterone or hydrocortisone.Experiments involving exposure of red cells to spirolactone and a cardiac glycoside simultaneously led to the conclusion that these substances do not have the same mechanism of action. The inhibition caused by spirolactone added to the inhibition due to a supramaximal concentration of ouabain (5 × 10^–4).

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Diese Arbeit wurde unterstützt durch ein Stipendium der CIBA für naturwissenschaftliche, medizinische und technische Forschung.     

Induction of the in vitro p-hydroxylation of14C-amphetamine stereoisomers in phenobarbital-treated rats

Summary The rate of p-hydroxylation of¹⁴C-(-)-amphetamine by liver microsomes was higher than that of (+)-isomer in phenobarbital-treated male rats. The apparent K_m values for (-)- and (+)-amphetamine hydroxylation were 4.54×10^–5 M and 2.27×10^–5 M respectively, in both treated and control animals.     

On the mechanism of the thermal decomposition of the peroxodisulphate ion in aqueous solution

Zusammenfassung Säurebildung als Zerfallsprodukt des Peroxodisulfations wurde in Gegenwart eines Radikalsammler mittels pH-stat-Technik untersucht: Die Säurebildung ist zu Beginn null. Dieses Ergebnis stützt die Theorie, wonach S₂O ₈ ^2– 2SO· ₄ ^– die Anfangsstufe der Zerfallsfolge ist.