Über eine Synthese von Ecdyson-3H und Ecdysteron-3H aus Cholesterin-3H in geschnürten Abdomina vonMamestra brassicae-Raupen

Summary After application of cholesterol-³H in ligated abdomina of 5th larva stages of the caterpillarMamestra brassicae ecdyson-³H and ecdysteron-³H was demonstrated in the abdomina 6 days after injection. The results show that in this case the synthesis of the moulting hormones from cholesterol occurs without participation of the prothoracic glands.     

Insomnia induced by P-chlorophenylalanine in cats. Its reversibility by intraventricular injections of indolamines

Intraventricular injection of 250 microgram of 5 HTP induces both slow wave and paradoxical sleep, after 20-60 min. latencies, in insomniac Cats pretreated with P-chlorophenylalanine. Direct injections of 5 HTP in several brain stem structures do not induce sleep. The long latency or paradoxical sleep induction and its suppression with chloramphenicol suggest that indolamines are not directly responsible for paradoxical sleep, but that they act by controlling the synthesis and/or the liberation in the periventricular system of some specific paradoxical sleep inducing factor.     

Post mortem increase of 5-hydroxytryptamine in rat brain after 5-hydroxytryptophan administration

Zusammenfassung Ratten mit und ohne Iproniazid-Vorbehandlung erhielten 30 min vor Dekapitation 5-Hydroxytryptophan (5HTP) i. p. Das intakte Hirn wurde bis zu 4 h bei 37° C, Zimmertemperatur und in 0·1n HCl aufbewahrt. In allen Fällen ergab sich eine starke postmortale 5-Hydroxytryptamin (5HT)-Vermehrung im Gehirn.Bei unbehandelten Kontrolltieren zeigte sich postmortal ein leichter 5HT-Abfall im Gehirn, der durch Iproniazid-Vorbehandlung aufgehoben wurde.     

Human platelet 5-hydroxytryptamine receptors: binding of [3H]-lysergic acid diethylamide (LSD). Effects of chronic neuroleptic and antidepressant drug administration

Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, the Bmax of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased the Bmax of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function.     

Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]GABA from rat brain homogenate

Rat brain homogenate was preloaded with [3H]noradrenaline or [3H]GABA and stimulated with high K+. Tetanus toxin and botulinum A neurotoxin partially prevent the evoked [3H]noradrenaline release in the same range of toxin concentrations starting below 10(-10) M. In contrast, release of gamma-amino butyric acid (GABA) is much more sensitive to tetanus than to botulinum A toxin.     

Etude autoradiographique de l'incorporation de la thymidine-3H,de l'uridine-3H et de la phénylalanine-3H dans les chloroplastes deClivia miniata etBilbergia sp.

Summary Mature chloroplasts ofClivia miniata etBilbergia sp. show the intensive incorporation of thymidine³H into DNA and uridine³H into RNA. On the contrary, phenylalanine³H is mostly incorporated in the proplastids.     

3[H]-Sulpiride labels mesolimbic non-dopaminergic sites that bind antidepressant drugs

3[H]-(-)-Sulpiride and 3[H]-spiperone binding was compared in rat amygdala, nucleus accumbens and striatum, using (+/-)-sulpiride to define specific binding. 3[H]-(-)-Sulpiride bound to twice as many sites in amygdala and nucleus accumbens as 3[H]-spiperone. 3[H]-(-)-Sulpiride binding was directed to these additional sites by using 1 microM spiperone to mask dopaminergic binding. The binding of 3[H]-(-)-sulpiride to these sites was high affinity, reversible, Na+-dependent, but not stereospecific. Metoclopramide, tiapride and antidepressant medications, but not other neuroleptics, ADTN, or serotonin displaced 3[H]-(-)-sulpiride binding to these sites. These data suggest that 3[H]-(-)-sulpiride labels mesolimbic sites other than dopamine receptors which may mediate antidepressant effects.     

Creatol (5-hydroxycreatinine), a new toxin candidate in uremic patients

Both 5-hydroxy-1-methylhydantoin (3) and the hitherto unrecognized 5-hydroxycreatinine (2-amino-5-hydroxy-1-methyl-imidazol-4(5H)-one or creatol) (6) can be isolated from the urine of uremic patients, in whom these compounds probably arise as oxidative metabolites of creatinine (1). The enhanced production of the well-known uremic toxin, methylguanidine (8), from creatinine (1) in such patients, almost certainly occurs via the newly recognized metabolite.     

Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]GABA from rat brain homogenate

Summary Rat brain homogenate was preloaded with [³H]noradrenaline or [³H]GABA and stimulated with high K⁺. Tetanus toxin and botulinum A neurotoxin partially prevent the evoked [³H]noradrenaline release in the same range of toxin concentrations starting below 10^–10M. In contrast, release of -amino butyric acid (GABA) is much more sensitive to tetanus than to botulinum A toxin.     

Iron-mediated inhibition of H+-ATPase in plasma membrane vesicles isolated from wheat roots

The mechanisms of iron-mediated inhibition of the H(+)-ATPase activity of plasma membrane (PM) vesicles isolated from wheat roots were investigated. Both FeSO(4) and FeCl(3) significantly inhibited PM H(+)-ATPase activity, and the inhibition could be reversed by the addition of the metal ion chelator EDTA-Na(2) or a specific Fe(2+) chelator, indicating that the inhibitory effect was due to specific action of Fe(2+) or Fe(3+). Measurement of the extent of lipid peroxidation showed that oxidative damage on the PM caused by Fe(2+) or Fe(3+) seemed to be correlated with the inhibition of PM H(+)-ATPase activity. However, prevention of lipid peroxidation with butylated hydroxytoluene did not affect iron-mediated inhibition in the PM H(+)-ATPase, suggesting that the inhibition of the PM H(+)-ATPase was not a consequence of lipid peroxidation caused by iron. Investigation of the effects of various reactive oxygen species scavengers on the iron-mediated inhibition of H(+)-ATPase activity indicated that hydroxyl radicals (*OH) and hydrogen peroxide (H(2)O(2)) might be involved in the Fe(2+)-mediated decrease in PM H(+)-ATPase activity. Moreover, iron caused a decrease in plasma protein thiol (P-SH), and Fe(3+) brought a higher degree of oxidation in thiol groups than Fe(2+) at the same concentration. Modification of the thiol redox state in the PM suggested that reducing thiol groups were essential to maintain PM H(+)-ATPase activity. Incubation of the specific thiol modification reagent 5,5-dithio-bis(2-nitrobenzoic acid) with the rightside-out and inside-out PM revealed that thiol oxidation occurred at the apoplast side of the PM. Western blotting analysis revealed a decrease in H(+)-ATPase content caused by iron. Taken together, these results suggested that thiol oxidation might account for the inhibition of PM H(+)-ATPase caused by iron, and that *OH and H(2)O(2) were also involved in Fe(2+)-mediated inhibition.     

Glucose-evoked recovery of hepatic thyroxine 5'-deiodinase independent of de novo protein synthesis in fasted rat

The glucose-evoked recovery of Type I thyroxine 5'-deiodinase activity in the hepatic microsomes of fasted rat was not inhibited by either cycloheximide, puromycin or actinomycin D during 3 h after glucose feeding; however, [3H]-leucine uptake by the liver or the hepatic microsomal fraction was significantly inhibited by cycloheximide and puromycin but not by actinomycin D. These results indicate that the glucose-evoked recovery of deiodinase activity may be independent of de novo protein synthesis.     

Bacterial lipopolysaccharide (LPS) enhances concanavalin A reactivity of thymocytes from the low-LPS-responder mouse strain C3H/Hej

Summary The capacity of LPS to enhance Con A reactivity of thymocytes was studied comparatively in the low-LPS-responder C3H/Hej mice and the high-LPS-responder CBA mice. The extent of synergism LPS+Con A was found similar in both strains.This work was supported by a grant from the INSERM (CRL: 76-5-101-1).     

Comparative study of the 3 beta-hydroxy-delta 5-steroid dehydrogenase activity of the mitochondrial and microsomal fractions of human and cat placentas

Delta 5, 3 beta hydroxysteroid dehydrogenase activity was studied on mitochondrial and microsomal fractions of human and cat placentas. This activity was assessed by measuring the rate of [3H] progesterone formation from [3H] pregnenolone and of [3H] delta 4-androstenedione from [3H] dehydroepiandrosterone (DHA), by a double isotope dilution method. Specific activities measured under initial velocity conditions were similar in both human and cat placentas. However, the kinetics of the reaction with DHA as substrate exhibit a zoological specificity.     

Autoradiographic localization of testosterone-3H in the female rat brain and estradiol-3H in the male rat brain

Zusammenfassung Eine halbe Stunde nach der i.v. Injektion wurde Testosterone-³H von den Nerven- und Glialzellen innerhalb des Gehirns der weiblichen Ratte und Estradiol-³H innerhalb des Gehirns der männlichen Ratte aufgenommen. Zwei Stunden nach der Injektion war die Aufnahme in hohem Masse nur noch in gewissen Teilen des hypothalamisch-limbischen Systems vorhanden.

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This investigation was supported by grants from NASA (No. NsG 496) and the John A. Hartford Foundation to Dr.H.-L. Teuber, and from the U.S. Atomic Energy Commission to Dr.J. Altman, both of the Massachusetts Institute of Technology, and the work was performed while the author was at M.I.T.     

Binding of [3H]GABA and [3H]muscimol to subcellular particles of a neurone-enriched culture of mouse brain

Summary Binding of [³H]GABA and [³H]muscimol, indicative of GABA-receptors, has been demonstrated in a neurone-enriched culture of embryonic mouse brain using a ligand-binding technique. Evidence is provided for the existence of different populations of GABA-receptors.This study was supported by C.N.R.S., ATP N^o 3356 and by Commissariat à l'Energie Atomique, Departement of Biologie. Thanks are due to Mlle Marie-Anne Frenkel for her excellent technical assistance.     

Identification of calcium antagonist receptor binding sites using (3H)nitrendipine in bovine tracheal smooth muscle membranes

(3H)Nitrendipine binding to the bovine tracheal muscle membrane at 25 degrees C was rapid, saturable (Bmax = 14.8 +/- 3.9 fmol/mg protein) and of high affinity (Kd = 0.15 +/- 0.04 nM). The rank order of Ca2+ antagonists competing for airway (3H)nitrendipine binding was nitrendipine not equal to nisoldipine not equal to nifedipine much greater than verapamil. Cromolyn, however, neither inhibited nor increased the binding.     

Synthesis of juvenile hormones in vitro by the corpora allata of 5th stage larva of Locusta migratoria migratorioides (R and F) (Insecta, Orthopteroida)]

Corpora allata of Locusta migratoria 5th stage larvae synthesize J.H.1, J.H.2 and J.H.3 in vitro. The C.A. of insects of different ages exbit different rates of J.H. synthesis. J.H.1 and J.H.2 synthesis is less than 1 ng/48 h/gland. During the same time the J.H.3 production may be as much as 25.6 ng/gland. J.H. synthetic activity is the same between right and left C.A. The release of J.H. from the C.A. occurs immediately following synthesis. These results are compared with in vivo haemolymphatic J.H. levels.     

Increase in in vivo (3H) spiperone binding in the rat hippocampal formation and striatum after repeated treatment with haloperidol

Summary An increase in in vivo (³H) spiperone binding was observed in rat hippocampal formation and striatum after repeated treatment with haloperidol. This suggests that in hippocampus as well as in striatum prolonged blockade of dopaminergic transmission by a neuroleptic agent results in the development of a supersensitivity of the dopamine receptors.Acknowledgments. We wish to thank Mrs J. Krauss for skillful technical assistance, Drs Helmut Bittiger and Rainer Ortmann for helpful discussions.