Effect of acute administration of Δ1-tetrahydrocannabinol on β-endorphin levels in plasma and brain tissue of the rat

Summary Acute treatment with ¹-tetrahydrocannabinol (¹-THC) elevated the concentration of -endorphin-like immunoreactivity (-ELIR) in plasma and in the hypothalamus, but not in the hippocampus of rats habituated to the injection procedure. These effects were not obtained with the psychotropically inert analog of (¹-THC), cannabidiol. In animals that had not been habituated to the injection procedure, placebo treatment induced a decrease in hippocampal -ELIR.The authors acknowledge the skillful technical assistance of Mrs Willeke Logtenberg.     

A major metabolite of Δ1-tetrahydrocannabinol reduces its cataleptic effect in mice

Summary The results described here demonstrate that THC-induced catalepsy in mice can be substantially inhibited by the prior administration of ¹-THC-7-oic acid, the major metabolite of THC in most species including humans. This raises the possibility that the intensity and duration of action of THC may depend to a large degree on the levels of this metabolite at the sites of action.We thank the National Institute on Drug Abuse for supporting this project by grants DA-02043 and DA-02052 and for supplying all of the cannabinoids. One of us (S.B.) is also the recipient of a Research Scientist Award from NIDA. We are grateful to Kristen Carlson and Thomas Honeyman for helpful suggestions in preparing this report.     

The partitioning ofΔ 1-tetrahydrocannabinol into erythrocyte membranes in vivo and its effect on membrane fluidity1into erythrocyte membranes in vivo and its effect on membrane fluidity1

Summary ¹-Tetrahydrocannabinol ( ¹-THC) has been quantified directly in erythrocyte membranes from drug-treated mice using gas chromatography/mass spectrometry. Concentrations of approximately 6 ng ¹-THC/mg membrane protein (10^–5 M) were found when effects of the drug on behavior were prevalent. At these concentrations the drug produced a decrease in membrane order as measured by ESR.This work was supported by grants from the Medical Research Council, the Wellcome Trust and the E. P. Abraham Cephalosporin Trust     

The effect of whole body röntgen irradiation on the megakaryocytic system in rat femur

Zusammenfassung Das hämopoietische Gewebe des Femurs junger Albinoratten wurde in einer Lösung, die 5% Na-Zitrat (1 Teil) und 0,7% Na-Chlorid (4 Teile) enthielt, suspendiert. Die Megakaryozyten, deren Durchmesser 24 µ überschritt, wurden in einer Bürker-Kammer gezählt. Der Effekt der Ganzkörperbestrahlung auf das Megakaryozytensystem wurde untersucht durch Festlegung des femoralen Megakaryozytengehaltes während den ersten 7 Tagen nach der Bestrahlung.     

Hepatic α-tocopherol binding protein in the rat: Absence of an effect of selenium deficiency on binding activity

Summary Selenium deficiency produces no effect on either the total content of or the binding properties of rat liver -tocopherol binding protein.     

The effect of bile salts on thyroxine 5′-monodeiodination in rat liver homogenate

Summary Unconjugated and conjugated bile salts inhibited the conversion of thyroxine to 3,3,5 triiodothyronine in rat liver homogenate.This work was supported in part by a grant from the Imanaga Foundation, Nagoya, Japan.     

Hashish: Synthesis of Δ9-tetrahydrocannabinol (THC), a metabolite ofΔ 9-THC1

Summary The synthesis of (±)-211-dihydroxy- ⁹-THC, a difunctionalized metabolite of ⁹-THC, is presented.Acknowledgment. This work was carried out with the support of NIDA Grant No. DA 00574. We are grateful to Mr. J. Coe for assistance with some of the experiments.     

Changes in rat erythrocyte membrane induced byΔ 1-tetrahydrocannabinol,scanning electron microscope study

Summary Although some biochemical dose-dependent effects are revealed in erythrocytes exposed to ¹ (THC) already at concentrations well below 10 M, marked morphological changes of the erythrocyte membrane become evident, by scanning electron microscopy, only at THC concentrations beyound 15 M. These observations provide evidence additional to previous chemical and physical studies, in which 15 M is found to be a critical concentration with respect to the effects of TCH on erythrocyte membrane.Acknowledgments. The authors are indebted to Prof. R. Mechoulam from the School of Pharmacy, The Hebrew University, Jerusalem, for providing the THC. The excellent technical assistance of Mrs R. Mordechai and of Miss L. Motola is gratefully acknowledged.     

The effect of γ-irradiation on the amount of 5-hydroxytryptamine in the gut and spleen in the early phase after irradiation

Résumé 24 et 48 h après irradiation- (900 r) la quantité de 5-hydroxytryptamine dans l'intestin du rat n'a pas changé de manière significative. La quantité de 5-hydroxytryptamine dans la rate du rat, exprimée par g de tissu frais a augmenté. Le prétraitement avec de la cystéamine abaisse nettement la quantité de 5-hydroxytryptamine dans la rate, après l'irradiation.     

Effect of tea consumption on the levels ofα-ketoglutarate and pyruvate dehydrogenase in rat brain

Summary Administration of tea to rats fed on a normal diet results in a marked drop in brain levels of total thiamine as well as of -ketoglutarate and pyruvate dehydrogenase activities. The patterns of decrease in both enzyme activities are similar to that of total thiamine content; they drop to about 65% of the control at 14–20 weeks after continuous consumption of tea.Supported by a grant from the International Foundation for Science (IFS), Sweden.     

Role of the conserved glutamine 291 in the rat γ-aminobutyric acid transporter rGAT-1

We investigated the role of the Q291 glutamine residue in the functioning of the rat γ-aminobutyric acid (GABA) transporter GAT-1. Q291 mutants cannot transport GABA or give rise to transient, leak and transport-coupled currents even though they are targeted to the plasma membrane. Coexpression experiments of wild-type and Q291 mutants suggest that GAT-1 is a functional monomer though it requires oligomeric assembly for membrane insertion. We determined the accessibility of Q291 by investigating the impact of impermeant sulfhydryl reagents on cysteine residues engineered in close proximity to Q291. The effect of these reagents indicates that Q291 faces the external aqueous milieu. The introduction of a steric hindrance close to Q291 by means of [2-(trimethylammonium)ethyl] methanethiosulfonate bromide modification of C74A/T290C altered the affinity of the mutant for cations. Taken together, these results suggest that this irreplaceable residue is involved in the interaction with sodium or in maintaining the cation accessibility to the transporter. Received 24 October 2005; accepted 11 November 2005     

Studies on the hypoglycemic effect of ‘Vincamin’

Zusammenfassung Nach Verabreichung von Vincamin sinkt bei akuten Versuchen an Ratten der Blutzuckerspiegel. Die nach Dextroseverfütterung verursachte Hyperglykämie wird durch Vincamin verhindert, der Blutzuckeranstieg jedoch bleibt nach Adrenalin unbeeinflusst.     

The effect of o,p′-DDD on the adrenal cortex in sheep

Summary The effect of o,p-DDD (200 mg/kg/day given p.o. for 100 consecutive days) on the sheep adrenal gland was studied. The results suggest that this ruminant species is highly resistant to the adrenocorticolytic activity of o,p-DDD when compared with dogs.This work was supported by a grant of Bristol Laboratories, Syracuse, New York 13201, USA.     

Perfusion studies employing α-C14 acetate to study the synergistic effect of cortisone and insulin on lipogenesis

Zusammenfassung Der vorliegende Aufsatz berichtet über Beobachtungen eines synergistischen Effektes von Insulin und Cortison bei der Fetts?uresynthese in der durchstr?mten Rattenleber. Dabei wurde Natrium-α¹⁴-C-acetat als Tracer verwendet und um Acetat bei der Biosynthese von Cholesterin und Fetts?uren aus dem Zweierbruchstück zu vertreten. Nach Lyophilisation der Leber, Extraktion und Fraktionierung der Lipide wurde gefunden, dass ins Cholesterin der mit Cortison behandelten Leber mehr radioaktiver Kohlenstoff eingetreten war, bei der Behandlung mit Insulin dagegen mehr in die Fetts?uren und schliesslich in dieselben doppelt soviel als ins Cholesterin bei Behandlung mit Insulin und Cortison zusammen. Der Anstieg nach Anwendung von Insulin allein dürfte auf Spuren von Nebennierenrindenhormonen zurückzuführen sein, welche noch in Leber und Blut vorhanden waren. Demnach darf angenommen werden, dass Cortison und Insulin, wenn sie gleichzeitig zur Wirkung kommen, von grossem Einfluss auf die Verwendbarkeit der Zweierbruchstücke sind. Der Anstieg der Cholesterinsynthese nach Behandlung mit Cortison ist durchaus bedeutungsvoll im Hinblick auf neuere Beobachtungen über Hypercholesterin?mien, welche w?hrend Cortisontherapie auftreten.      

Leão's spreading depression in the cerebellum of rat

Zusammenfassung Ischämie ruft in der Kleinhirnrinde eine ähnliche Depolarisation hervor wie in der Grosshirnrinde. Durch lokale KCl-Applikation erhält man in der Kleinhirnrinde langsame Potentialwellen, die in Amplitude und Ausbreitungsgeschwindigkeit der «spreading depression» vonLeão in der Grosshirnrinde entsprechen. Ischämie und lokale Applikation von 2,4-Dinitrophenol bewirken in beiden Rindengebieten gleiche Verschiebungen der Kaliumionen.     

Effects of two kinds of social deprivation on testosterone and estradiol-17β plasma levels in the male rat

Summary The effect of complete and tactile isolation on plasma testosterone and estradiol-17 was studied in male rats at the age of 60 and 180 days. A decrease in the plasma levels of the two hormones was observed.     

The effect of αB-crystallin and Hsp27 on the availability of translation initiation factors in heat-shocked cells

The mechanism of the translational thermotolerance provided by the small heat shock proteins (sHsps) αB-crystallin or Hsp27 is unknown. We show here that Hsp27, but not αB-crystallin, increased the pool of mobile stress granule-associated enhanced green fluorescent protein (EGFP)-eukaryotic translation initiation factor (eIF)4E in heat-shocked cells, as determined by fluorescence recovery after photobleaching. Hsp27 also partially prevented the sharp decrease in the pool of mobile cytoplasmic EGFP-eIF4G. sHsps did not prevent the phosphorylation of eIF2α by a heat shock, but promoted dephosphorylation during recovery. Expression of the C-terminal fragment of GADD34, which causes constitutive dephosphorylation of eIF2α, fully compensated for the stimulatory effect of αB-crystallin on protein synthesis in heat-shocked cells, but only partially for that of Hsp27. Our data show that sHsps do not prevent the inhibition of protein synthesis upon heat shock, but restore translation more rapidly by promoting the dephosphorylation of eIF2α and, in the case of Hsp27, the availability of eIF4E and eIF4G. Received 9 December 2005; received after revision 16 January 2006; accepted 23 January 2006     

Age-related differences in the urinary excretion of prostaglandin F2α catabolites in the rat

Summary Tritium-labelled PGF₂ was administered i.v. into rats of varying ages (2, 4, 6 weeks and adult). Urine was collected and assayed for radioactive products by thin-layer-chromatography. Results showed a distinctly different urinary profile between the 2-week-old and the adult rat. While the urinary pattern from the 2-week-old rat gave a single less polar product than PGF₂, the pattern from the adult rat gave products more polar than PGF₂. Urine from the 4- and 6-week-old rats gave a mixture of these types of products. These results indicate that some prostaglandin catabolic pathway (likely the -oxidative system) is activated in vivo within the 4–6-week postnatal period in the rat.Supported by a grant (MT-4181) to C.P.-A. from the Medical Research Council of Canada.This study is in partial fulfillment of the requirements for a Ph.D. degree in the Department of Pharmacology, University of Toronto.