In vitro metabolism of progesterone by the adrenals of spontaneously hypertensive rats

Zusammenfassung Der Einbau des¹⁴C-Progesterons in Corticosteroide bei Nebennierensegmenten von Wistar-Ratten mit spontaner Hypertonie unterscheidet sich in nichts vom Einbau bei Nebennieren der Kontrollratten, was im Gegensatz zu Befunden mit regenerierten Nebennieren steht. Eine kausale Beziehung zwischen Nebennierenrindenfunktion und spontanem Hochdruck scheint ausgeschlossen zu sein.

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Dr. M. K.Birmingham is a Medical Research Associate of the Medical Research Council of Canada. This work was supported by grants from the Medical Research Council of Canada and the 33rd Degree Scottish Rite Committee for Research in Dementia Praecox. The authors thank Dr. R. A.Cleghorn for his interest in this project.     

Inactivation of yeast glucose-6-P dehydrogenase by aspirin

Summary Glucose-6-P dehydrogenase is irreversibly inactivated by treatment with Na salts of aspirin. Kinetic data show that 1 molecule of aspirin reacts with each active unit when the enzyme is inactivated. The rate of inactivation is enhanced with increasing pH but is reduced in the presence of glucose-6-P or NADP⁺. Na salicylate fails to inactivate the enzyme.This work was supported by grant RR-8006 from the General Research Branch, Division of Research Resources, NIH (USA).     

Formation of 4-ketocyclophosphamide by the oxidation of cyclophosphamide with KMnO4

Zusammenfassung Oxydation des (³²P) Cyclophosphamides durch KMnO₄ in Wasser oder Aceton führt zu 4-Ketocyclophosphamid und einem N-dechloroäthylierten Derivat des Cyclophosphamides, beides bekannte Metaboliten der Droge. Die Auftrennung der Produkte gelingt durch Dünnschichtchromatographie und die Richtigkeit der Strukturen wurde durch Massenspectrometrie nachgewiesen.

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Acknowledgments. This investigation was supported by grants to the Chester Beatty Research Institute (Institute of Cancer Research: Royal Cancer Hospital) from the Medical Research Council and Cancer Research Campaign. The A.E.I. MS-12 mass spectrometer was purchased on a special grant No. G969/189/C from the Medical Research Council. The work was carried out partly during the tenure of a Ludwig Fellowship awarded by Cancer Research Institute. The interest of ProfessorA. B. Foster and Dr.T. A. Connors in this work, and the skilled technical assistance of Mr.M. H. Baker, are gratefully acknowledged.     

Thiamine transport by human intestine in vitro

Summary Surgical specimens of human gastrointestinal mucosa and muscle were incubated in vitro with thiaminethiazole-2-¹⁴C. Labelled thiamine uptake was uphill in mucosal tissues and downhill in muscle. Small intestinal mucosa accumulated labelled thiamine in a phosphorylated form, while gastric and colonic mucosa, as well as muscular layers of all gastrointestinal segments studied, did not.This work was supported in part by a grant from the Italian Research Council, Rome, Italy.     

An attempt at colonization of WvWv anemic mice by rat hemopoietic tissue

Zusammenfassung Speziesfremdes, hämopoietisches Gewebe wurde neugeborenen, anämischen W^vW^v-Mäusen implantiert. Die Folgen davon werden analysiert.

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This work was supported by the Spastics Society and the Medical Research Council.     

Effect of low density lipoprotein on proteoglycan synthesis by aorta cells in culture

Summary Increasing the content of human serum low density lipoprotein in the growth medium led to greater incorporation of³⁵S-sulfate into proteoglycan (mostly into dermatan sulfate) by primary aorta cells but did not affect similar incorporation by fibroblast cells. These results suggest a mechanism which can explain the increased deposition of lipid in aorta due to hyperlipidemia.Acknowledgements. This work was supported by a Fort Polk-American Heart Association-Louisiana, Inc. Research Award.     

Inhibition of platelet ADP and serotonin release by carbon monoxide and in cigarette smokers

Summary The release of¹⁴C-serotonin by ADP, epinephrine and arachidonic acid and the release of ADP by kaolin were measured in normal platelets in the presence and absence of carbon monoxide and in smokers' platelets. It is shown that carbon monoxide inhibits significantly the platelet release reaction. This function is also decreased in platelets obtained from heavy cigarette smokers.This work was supported by Veterans Administration Research Fund 8073-01.     

Enhanced excitability in locust muscle fibres induced by calcium free saline

Summary The membrane of locust muscle fibres normally exhibits a graded electrical response to outward current pulses of increasing strength. On removal of Ca⁺⁺ ions from the external medium, these fibres are shown to exhibit depolarizing membrane responses of variable time course and duration. These responses are abolished in Na⁺-free solutions, and by the addition of Mn⁺⁺ ions.D.A.M. was the recipient of a Royal Society and Science Research Council European Exchange Fellowship. We thank the Centre for Overseas Pest Research, Kensington for supplying the locusts.     

Relaxation by glucagon of potassium contracture in cat ventricle

Summary Glucagon reduces K⁺-contracture, increases peak active force, but does not alter time to peak force and relaxation of the isometric twitch of cat ventricle.This study was supported by a grant-in-aid from the Florida Heart Association-Suncoast Chapter, National Institute of Health Research grant HL 19044 and NSRA Awards HL 05849 and HL 07188.The authors wish to thank Mr William Fitterman for his valuable technical and illustrative assistance.     

Conversion of testosterone to androstenedione by liver homogenates of testicular feminized mice

Summary Liver homogenates of testicular feminized (Tfm) mice carrying the protective (o^hv) gene were found to be less capable of converting testosterone to androstenedione than Tfm without the protective gene.This work was supported by the Medical Research Council of Canada, No. MT 4192 and Ortho Pharmaceutical Company.     

Selective antagonism by Mg2+ of amino acid-induced depolarization of spinal neurones

Summary In the isolated frog or rat spinal cord, low concentrations of Mg²⁺ (0.5–1.00 mM) markedly depress, in a substantially Ca²⁺-independent manner, ventral root depolarizations produced by dorsal root stimulation and by certain amino acids (e. g. N-methyl-D-aspartate and L-homocysteate) but do not depress depolarizations produced by other excitatory amino acids (e. g. kainate and quisqualate). L-Aspartate-induced depolarizations are more sensitive to Mg²⁺ then are L-glutamate-induced depolarizations.Acknowledgment. We thank D. J. Oakes for skilled technica assistance. This work was supported by the Medical Research Council.     

The metabolism of methadone by cultured mammalian cells

Summary Rat hepatoma tissue culture cells and mouse leukemic cells were found to metabolize [1-³H] methadone to at least 2 unidentified radioactive compounds. These results suggest that cultured cells may be useful models for studying methadone metabolism by specific cell types.This study was supported by United States Public Health Service Research Grant No. MH 15622. The illustrations were prepared by Diane J. Kastelic.     

Nuclear localization of aldosterone in rat brain cells assessed by autoradiography

Summary Autoradiographic studies with³H aldosterone demonstrate nuclear concentration of hormone in neurons of the hippocampus, septum, allocortical regionss and brain stem reticular formation and motor nuclei of cranial nerves and in the meninges. The results suggest that mineralocorticoids have wide ranging effects on different parts of the central nervous system.This work was supported by the Medical Research Council of Canada and by PHS grant NS09914. We thank Ms Brenda McClain for technical assistance.     

High affinity of quinidine for a stereoselective microsomal binding site as determined by a radioreceptor assay

Summary The techniques of the radioreceptor binding assay were applied to detect stereoselective binding of quinidine and quinine to a site on human liver microsomes. Binding of³H-dihydroquinidine was 50% inhibited by 20–100 nM quinidine, while its enantiomer quinine did not displace the³H-ligand at concentrations up to 500 nM. This stereoselectivity agreed with the affinity values measured by functional enzyme assays of cytochrome P450 activity using sparteine or debrisoquine as substrates.Acknowledgments. We thank C. Ulpian for advice and assistance. We also thank Dr M. Robinette of Metro Organ Retrieval and Exchange and Dr T. Inaba for making human hepatic tissue available. This work was supported by grants from the Medical Research Council of Canada.     

Inhibition of neurotensin (NT)-induced glucagon release by [D-Trp11]-NT1

Summary A synthetic analog of neurotensin (NT), [D-Trp¹¹]-NT, antagonized NT-induced hyperglucagonemia and hyperglycemia, and also NT-induced glucagon release from pancreatic islets in rats.This work was supported in part by a grant from the Imanaga Medical Research Foundation, Nagoya, Japan. Address for reprint requests: M.U., Department of Surgery, National Nagoya Railway Hospital, Taiko 1-chome, Nakamura-ku, Nagoya 453, Japan.     

Guanylate cyclase stimulation by nitro-compounds is dependent on free Ca2+1

Summary The stimulatory effect of nitro-compounds on arterial and hepatic guanylate cyclase became significantly depressed at 0.2 M and higher concentration of free Ca²⁺. The basal enzyme activity proved to be Ca²⁺-independent.This study was supported by the Anton Dreher-Foundation for Medical Research.     

Survival enhanced by skin-wound trauma in mice exposed to60Co radiation

Summary A 4%-body-surface skin wound given 24 h before exposure of mice to⁶⁰Co radiation raised the LD 50/30 from 825 to 975 rads, resulting in a dose reduction factor of 1.2. Enhanced survival of mice wounded before radiation was independent of extramedullary splenic myelocytopoiesis.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under research work unit 8324-60406. The views presented in this paper are those of the authors. No endorsement by the Defense Nuclear Agency has been given or should be inferred.Research was conducted according to the principles enunciated in the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Research, National Research Council.     

Changes in blood-brain permeability resulting from d-amphetamine, 6-hydroxydopamine and pimozide measured by a new technique

Summary A new technique is described for measurement of diffusion across the blood-brain barrier using intraventricularly administered⁶⁸Ga-EDTA, and determining loss from the brain with a scintillation camera. Repeated injections via permanent cannulas showed that the diffusion half-time was reduced to 50% of control values after intraventricular d-amphetamine and 6-hydroxydopamine; pimozide had no effect.Acknowledgment. This work was supported by the Division of Biomedical and Environmental Research of the US Department of Energy, and the Deutsche Forschungsgemeinschaft.     

Ureteral contractions induced by rat urine in vitro: Probable involvement of renal kallikrein

Summary Rat urine, even at a 110 final dilution in Tyrode's solution, stimulates contraction of the ureteral musculature in vitro. This effect can be ascribed to the presence of kallikrein or a kallikrein-like enzyme in urine. Isometric contractions of ureters were prevented by previous addition of aprotinin to the organ bath. Urine also lost its activity after inactivation of enzymes by heat or acid treatment.Acknowledgments. Aprotinin (Trasylol^®) was kindly supplied by Baypropharm, Köln, W.-Germany. This work was supported by the German Research Foundation (SFB 90).     

Specific inhibition of a calcium dependent activation of brain cyclic AMP phosphodiesterase activity by vinblastine

Summary Vinblastine selectively inhibits the activation of brain cyclic AMP phosphodiesterase activity by Ca⁺⁺-protein activator (50% inhibition by 2×10^–5 M). This inhibitory effect was reversed by excessive amounts of the activator, whereas large quantities of Ca⁺⁺ caused only a slight suppression of the vinblastine effect. This result of vinblastine suggests a new site of its action and also suggests the possible role of protein activator, phosphodiesterase proteins or cyclic nucleotides in the previously known effects of vinblastine in vivo and in vitro.Our thanks to Drs A. R. Rhoads, C. B. Klee and R. A. Fergusson for analyzing PA preparations by gel electrophoresis and gel electrofocusing, and to Drs A. A. Suran and D. Soifer for their valuable critiques to this work. This work was partly supported by Biochemical Research Support Grant No. 5SO7RRO5361 to K.W. and Graduate Training Grant No. 5TO2GMO500002 to W.L.W. from NIH.