The biliary excretion of [3H] lysergic acid diethylamide in Wistar and gunn rats

Summary The biliary excretion of [³H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.     

The biliary excretion of [3H] lysergic acid diethylamide in Wistar and Gunn rats.

The biliary excretion of [3H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.     

Decrease in [3H]ouabain binding sites in heart and brain from spontaneously hypertensive rats

Summary A decrease in the number of binding sites (B_max) for [³H]ouabain was observed in the heart (37%) and the brain (22%) of spontaneously hypertensive rats (SHR) when compared with age-matched control Wistar Kyoto rats. No variation was detected in the affinity constant (K_D).     

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.     

The local anesthetic potency of norcocaine,a metabolite of cocaine

Summary The local anesthetic effects of cocaine and one of its main metabolites norcocaine, were investigated comparatively on isolated ganglion cells of the marine gastropod,Aplysia californica. During a 1-hour-period, different action potential parameters such as amplitude, duration, maximum rate of rise were observed, which demonstrated that norcocaine exhibits a higher local anesthetic potency than cocaine.Acknowledgments. The authors are grateful to Dr M. R. Klee and Dr M. R. Park for helpful discussion. The work was partly supported by Österreichischer Fonds zur Förderung der wissenschaftlichen Forschung     

The localization of [3H]-desipramine in central nerve terminals studied with electron microscope autoradiography and subcellular fractionation

Summary The cellular and subcellular distribution of [³H]-desipramine (DMI) in rat brain was studied by electron microscope (EM) autoradiography and by subcellular fractionation. A considerable proportion of label was found to be bound to the membranes of presynaptic nerve terminals, as well as to sites inside those terminals.Acknowledgment. The authors are most grateful to Mr and Mrs Gudelsky for their generous support.     

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.     

The localization of [3H]-desipramine in central nerve terminals studied with electron microscope autoradiography and subcellular fractionation.

The cellular and subcellular distribution of [3H]-desipramine (DMI) in rat brain was studied by electron microscope (EM) autoradiography and by subcellular fractionation. A considerable proportion of label was found to be bound to the membranes of presynaptic nerve terminals, as well as to sites inside those terminals.     

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.     

Multiple daily amphetamine administration decreases both [3H]agoinst and [3]antagonist dopamine receptor binding

Summary Multiple daily amphetamine injections in rats decreased both [³H]agonist as well as [³H]antagonist striatal dopamine receptor binding. Concurrently, these animals exhibited a decrease in striatal dopamine concentration and, paradoxically, an enhancement of behavioral responsivity.This study was supported by PHS grant MH32990 to I.C. and DA0156805 to D.S.I. Creese and D. Segal are the recipients of the RSDA grants MH00316-01 and RSDA MH70183-08, respectively.     

Presence of specific binding sites for [3H]sarcophytol-A in cultured human skin fibroblasts

Summary The presence of specific binding sites for [³H]sarcophytol-A in human skin fibroblasts was examined using biochemical and morphological methods. The displacement studies clearly revealed that high (K_D=31.0 nM) and low (K_D=6.05 M) affinity sites were present in the intact cells. Moreover, autoradiographic studies using light microscopy revealed that the specific binding sites may exist in boththe cytoplasm and the nuclei.     

Colchicine induced interchanges in chillies (Capsicum annuum L.)

Summary Seeds ofCapsicum annuum L. cultivar cerasiformies were treated with 0.4 and 0.2% aqueous colchicine solution for 24 and 72 h respectively. Tetraploids were not realized; instead, interchange heterozygosity was observed in several plants in 0.4% treatment. The interchanges varied from 1 to 3 per plant. It is presumed that colchicine has induced chromosome breaks.     

Involvement of H1 receptors in the central antinociceptive effect of histamine: Pharmacological dissection by electrophysiological analysis

Intracerebroventricular (i.c.v.) administration of histamine (HA, 0.025–0.1 M/rat) to arthritic rats induces a dose-related inhibition of the neuronal thalamic firing evoked by peripheral noxious stimuli. To characterize the type(s) of HA receptors involved in this depressing activity of the amine we used electrophysiological techniques to examine the effects of i.c.v. administration of H₁ and H₂ agonists and antagonists on the spontaneous and evoked nociceptive firing of the thalamic neurons in rats rendered arthritic by Freund's adjuvant. The H₁ agonist 2-pyridylethylamine (0.4–1.0 M/rat, i.c.v) displayed a dose-dependent antinociceptive effect very similar to that of HA, while the H₂ agonist dimaprit (0.05–0.2 M/rat, i.c.v.) did not modify thalamic firing. Neither mepyramine (H₁ antagonist, 0.1 M/rat, i.c.v.) nor zolantidine (H₂ antagonist, 0.01 M/rat, i.c.v.) modified the evoked firing of rat thalamic neurons. When administered before HA (0.1 M/rat, i.c.v.) mepyramine but not zolantidine was able to inhibit the antinociceptive effect of HA. On the basis of the present electrophysiological results, we suggest that a specific interaction of histamine with H₁ receptors may be important for its antinociceptive effect on afferent peripheral inputs to the thalamus.     

LSD: The distribution of [3H]LSD in the reproductive system of the male rat and placental transfer in the female rat

Summary After administration of [³H]LSD to male rats, radioactivity was present in all tissues of the reproductive system, notably associated with spermatozoa in the epididymis. In addition, in pregnant rats LSD and/or metabolites readily crossed the placental barrier.     

Comparative incorporation of uridine-3H into nucleolar RNA of mouse subcutaneous and skin tissues at early times after 20-methylcholanthrene administration

Summary A single s.c. injection of 20-methylcholanthrene (1 mg in 0.2 ml olive oil) is found to stimulate the relative uptake of uridine-³H by the skin and the s.c. tissue 17- and 3fold respectively, 24 h post-administration.     

Na*-independent binding of [3H] muscimol to a membrane fraction of the brains of normal and dwarf mice

Summary Although their body weights were decreased by about 77% and their brain weights by about 30%, high-affinity [³H] muscimol binding to a cerebral membrane fraction was not altered in hereditary pituitary dwarf mice. Marked changes in the level of pituitary growth-associated hormones do not appear to be associated with a change in cerebral GABA-receptors.Supported by a UNESCO/IBRO Fellowship. Permanent address: Semmelweis University Medical School, 1st Institute of Biochemistry, Budapest, Hungary.     

The metabolism of the soil fumigant 1,2-dibromo-3-chloropropane in the rat

Summary The soil fumigant 1,2-dibromo-3-chloropropane (I) undergoes hydrolysis in the rat to a series of epoxide metabolites. Alkylation of glutathione by these epoxides produces 2 urinary metabolites identified as the mercapturic acids VI (R=COCH₃) and VII (R=COCH₃). Hydrolysis of the epoxides produces the male antifertility agentsa-chlorohydrin (IX, X=Cl) anda-bromohydrin (IX, X=Br) which are oxidatively metabolized to oxalic acid (XII), thus causing renal damage. These metabolic pathways can explain the toxic nature of the fumigant as a carcinogen, a male chemosterilant and as an agent causing kidney damage.This work was supported in part by the National Health and Medical Research Council of Australia.     

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.     

[3H]Formate incorporation into liver nucleic acids of chick. Relationships between orotic acid and vitamin B12

Riassunto E' stato studiato l'effetto dell'acido orotico sull'incorporazione di formiato-H³ nei nucleotidi liberi totali e negli acidi nucleici presenti nelle frazioni subcellulari del fegato di pulcino carente di B₁₂. La maggiore attività specifica dell'RNA nucleare e ribosomiale che si osserva negli animali trattati con acido orotico come in quelli trattati con vitamina B₁₂ potrebbe essere considerata l'espressione di una più elevata sintesi di RNA messaggero determinata da queste due sostanze.

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This investigation was supported by a grant from Consiglio Nazionale delle Ricerche, Roma.