Effects of propafenone on TEA-induced action potentials in vascular smooth muscle of canine coronary arteries

Summary The Ca⁺⁺-dependent, TEA-induced action potential is blocked by propafenone in a dose-dependent manner. Such results suggests that in coronary arterial smooth muscle one mechanism of action of propafenone is to inhibit Ca⁺⁺ inward current.This research was supported by a grant from the Tennessee Affiliate of the American Heart Association and VA grant No. 1A (74)111-430100). The authors wish to thank Dr Gerhard Pfennigsdorf for supplying us with propafenone. We also wish to thank Ms Penny Williams for her technical assistance.     

Ca-antagonistic substance from soft coral of the genusSarcophyton

Summary A 14-membered ring diterpenoid named cembrane, possessing Ca-antagonistic action on the isolated rabbit aorta, has been isolated from a soft coral of the genusSarcophyton, and its structure established by X-ray and spectroscopic data.The authors thank Mr. Z. Nagahama (Okinawa) for collection of soft corals, Miss R. Abe (the present institute) for her skillful assistance, and Dr. T. Higashijima, Prof. T. Miyazawa (Tokyo University), Mr. T. Hayase and Dr. H. Ohtani (Mitsubishi Chemical Industries Ltd) for¹H and¹³C NMR-measurements.     

Purification from human plasma of endogenous dodium transport inhibitor(s)

Summary Na⁺, K⁺-ATPase inhibitors extracted from plasma of healthy human subjects displaced³H-ouabain binding to human erythrocytes and inhibited the Na⁺ efflux catalyzed by the Na⁺, K⁺-pump and unexpectedly the Na⁺, K⁺-cotransport system without alteration of the Na⁺, Na⁺-exchange or the Na⁺ passive permeability. This suggests the presence in healthy human plasma of endogenous factors with ouabain-like and furosemide-like activities.Acknowledgments. We are indebted to Dr M. A. Devynck for her advice on chemical measurements and to Dr R. P. Garay for his help with flux measurements     

The in vitro characterization of the inhibition of mouse brain protein kinase-C by retinoids and their receptors

Summary The mechanism of the in vitro inhibition of Ca²⁺-, phosphatidylserine-dependent protein kinase C (PK-C)² by the purifiedholo (ligand-saturated) forms of cellular retinol-binding protein (cRBP) and cellular retinoic acid-binding protein (cRABP) was studied. We report here that i) the PK-C-inhibitory action ofholo-cRBP andholo-cRABP is due to their respective ligands, all-trans-retinol and all-trans-retinoic acid; ii) the reduced phosphorylation of theholo-retinoid-binding proteins and brain cytosolic proteins is not the result of a retinoid-induced soluble phosphatase or protease activity; iii) retinoids reduce PK-C affinity for calcium and phosphatidylserine in vitro; and iv) the structure-function activity of the retinoids and the specific interaction of these effect of retinoids on plasma membrane-associated PK-C activity pays a significant role in defining the early epigenetic aspects of PK-C-dependent tumor promotion and may be a physiological mechanism by which retinoids induce terminal differentiation in cell types that do not express soluble retinoid-binding proteins.We would like to thank Dr L.M. De Luca (NIH, USA) for his contribution of retinylphosphate, Dr H.N. Bhagavan (Hoffmann-La Roche) for his contribution of the arotinoids, and Merrill-Dow Corp. for their contribution of difluoromethylornithine. This work was supported by NIH Grants CA-34968, CA-07175, CA-22484, and CA-09020.     

Net ATP synthesis by running the red cell calcium pump backwards

Summary Ca²⁺ loaded inside-out vesicles from human red blood cells, yielding Ca²⁺ into a Ca²⁺ free medium with 4 mM EGTA, 2 mM ADP and 10 mM phosphate, produced an excess of 14.9 pmoles · min^–1 · (mg protein)^–1 of ATP compared to controls in which the transmembrane Ca²⁺ gradient was abolished by the ionophore A 23 187.We are obliged to Dr H. Fey and Miss H. Pfister (Veterinarybacteriological Institute Bern) and Dr H. Porzig (Pharmacological Institute Bern) for help and advice.     

The effect of the phytoalexins,lubimin, (−)-maackiain,pinosylvin, and the related compounds dehydroloroglossol and hordatine M on human lymphoblastoid cell lines

Summary We have tested the effect of the phytoalexins lubimin, (–)-maackiain and pinosylvin and the related compounds dehydroloroglossol and hordatine M on the growth of the human lymphoblastoid cell lines Molt and Raji. (–)-maackiain, pinosylvin and dehydroloroglossol showed significant growth inhibitory action on the cells. Suppression of [³H] thymidine and [³H] leucine uptake was tested and noted in pinosylvin and dehydroloroglossol. The phytoalexins and related compounds are widespread in plants and provide a potential source of antineoplastic substances.We would like to acknowledge the assistance of J. Hux in preparing the phytoalexins and related compounds. This work was supported by a grant from National Health and Welfare Canada. Correspondence to Dr. L. Skinnider, Department of Pathology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7M OWO.     

Chromsome aberrations in cattle raised on bracken fern pasture

Summary Thirteen cows maintained on natural bracken fern (Pteridium aquilinum) were analyzed cytogenetically. The frequency of structural chromosome aberrations detected in peripheral blood cells was significantly higher when compared to that detected in animals raised on pasture containing no bracken fern. We discuss the clastogenic action of fern and its synergistic action with infection by type 2 and 4 papilloma virus in the same animals.Acknowledgments. We are grateful to Dr F. J. Benesi, Dr J. L. Guerra and Dr I. L. Sinhorini for performing some of the clinical and pathological analyses; O. P. Ferraz, L. A. Tadeu Dias, L. F. Feitosa and A. M. N. Paiva for technical assistance; and to Dr N. H. C. Castro and Dr C. de Araujo Peres for critical and statistics review, respectively. Research was supported by CNPq FAPESP and CAPES.     

Abnormal organization of ovarian follicles in the mutantl(1)su(f) mad-ts ofDrosophila melanogaster

Summary The morphology of ovarian follicles in the temperature-sensitive female-sterile mutantl(1)su(f) ^mad-ts has been studied by means of light and electron microscopy. As the follicle cells gradually degenerate at the restrictive temperature (29°C) the follicles become increasingly disorganized with respect to shape and polarity.Acknowledgments. This work was supported by the Deutsche Forschungsgemeinschaft (SFB 46). We wish to thank Mrs R. Koppa for excellent technical assistance and Mrs G. Mahlke for photographic work. We are also indebted to Dr D. Zissler, Dr E. Gateff and Prof. K. Sander for many helpful suggestions.     

The absolute configuration of SU 23397: A novel neuroleptic agent

Summary The absolute configuration of a novel chiral neuroleptic agent SU 23397 (I) was determined by ORD comparison of (+)-5-methoxy dihydro coumarilic acid (VIII), a synthetic precursor of SU 23397 (I), with (+)-dihydro coumarilic acid, whose absolute configuration is known⁹. This assignment was confirmed by oxidative degradation of (+)-5-methoxy dihydro coumarilic acidVIII tod-(+)-malic acid.Acknowledgments. We wish to acknowledge and thank Dr J. Karliner, Ciba-Geigy Corporation, Ardsley, New York, for the ORD curves. We thank Dr Max Wilhelm for support and encouragement.     

9,10-Dihydroergotamine: Production of antibodies and radioimmunoassay

Summary Antibodies against 9,10-dihydroergotamine (DHE) were produced by immunizing rabbits with a conjugate of 6-nor-6-carboxymethyl-9,10-dihydroergotamine and bovine serum albumin. A highly specific and sensitive radioimmunoassay for DHE has been developed.We are greatly indebted to Dr.T. Fehr for the synthesis of 6-nor-6-carboxymethyl-9,10-dihydroergotamine, and to Dr.E. Schreier for providing us with 9,10-dihydroergotamine-[13-³H]-base of high specific activity.     

Amantadine modulates phencyclidine binding site sensitivity in rat brain

Summary Amantadine, an antiviral drug with various CNS effects, significantly increases the affinity of the [³H] PCP receptor in rat brain. Rimantadine, an analogue of amantadine devoided of CNS effects, does not have any affect on the [³H] PCP receptor. These results may suggest that some of the CNS actions of amantadine are related to an interaction with the PCP receptor.Acknowledgments. We thank Dr W. K. Schmidt (E.I. Dupont, Newark, Delaware) for gifts of amantadine and rimantadine. Dr R. Quirion is a fellow of the Medical Research Council of Canada.     

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.     

Methyllycaconitine,a naturally occurring insecticide with a high affinity for the insect cholinergic receptor

Summary Studies of extracts ofDelphinium seeds, long known to be insecticidal, revealed that a principal insecticidal toxin was methyllycaconitine, which is shown to be a potent inhibitor of -bungarotoxin binding to housefly heads (K_inh=2.5×10^–10±0.5×10^–10M).Calgary for gifts of MLA, citrate and lycoctonine, and Dr W. Bowers of the University of Arizona for the original extract ofDelphinium seeds. We would also like to acknowledge the able technical support of Ms C. Dushin, Mr E.L. Bowman, Dr C. C. Gagne, Mr R. F. Borysewicz and Dr P. Mowery for his assistance in obtaining and interpreting the carbon-13 NMR spectra.     

Reversion of virus N-1 resistant mutant of blue-green algaNostoc muscorum

Summary The reversion of N-1 virus resistant strain of the algaNostoc muscorum was studied by inoculating parent virus in the resistant culture at various incubations. A fraction of virus resistant cells reverted to wild sensitive type with the reversion rate of 3.99×10^–6/cell/generation.We gratefully acknowledge Dr H.K. Pande and Dr S. Patnaik, Crops and Soils Division.     

Mutagenicity testing of 3 hallucinogens: LSD,psilocybin and‡ 9-THC using the micronucleus test

Summary Using the micronucleus test as a screening method for mutagenic activity, no significant increase in the number of micronuclei was found when LSD, psilocybin or ⁹-THC were administered in 3 logarithmically increasing doses to mice. Azathioprine (Imuran^®), given as a positive control, caused a statistically significant increase in micronucleated cells.Acknowledgment. The expert technical assistance of Mr Joop Branger is greatfully acknowledged. We thank Prof. Dr C. A. Salemink, University of Utrecht, for the supply of the THC, and Dr J. Fokkens, National Institute of Public Health, for preparing the solutions.     

Effective dose present in cockroach larvae exposed continuously to a juvenile hormone active insect growth regulator

Summary Larvae of the German cockroach exposed to filter paper impregnated with juvenile hormone (JH) active substance contain, at the middle of the last instar, about one-hundredth of the dose applied to 1 cm². The amount of metabolized substance rises sharply before and disappears rapidly after the ecdysis into the supernumerary instar.Acknowledgments. We wish to express our thanks to Prof. Dr H.A. Schneiderman, Dr W. Vogel and Dr P.A. Vonder Mühll for stimulating discussion and to Mr M. Gruber for correction of the text.     

Activation and specificity of alkaline phosphatase of a mineralizing collagen-rich system

Summary Alkaline phosphatase from tibia tendon ofMeleagris gallopavo L. was highly purified. The enzyme activation by different ions was measured. Mg²⁺ showed a high activation with a broader spectrum of phosphomonoester hydrolization. The in vivo Mg²⁺ concentration was an optimum for in vitro activation.Dedicated to Prof. Dr. G. Pfefferkorn on the occasion of his 65^th birthday.We thank Deutsche Forschungsgemeinschaft for support.     

Intracellular free calcium as a pathogen in cell damage initiated by the immune system

Summary It is proposed that the earliest intracellular event induced by the action of complement is an increase in cytosolic free calcium, which can occur in the absence of lysis. This increase causes morphological and chemical changes in the cell and also results in modified responses to physiological stimuli.In this article the term free calcium is used to mean ionised calcium, i.e. Ca²⁺, not bound to ligands.Acknowledgments. We are grateful to members of the Welsh National School of Medicine, University of Cambridge, School of Clinical Medicine, and the Marine Biological Association Laboratory, Plymouth, for valuable advice and discussions. In particular we thank our colleagues Dr M.B. Hallett, Dr P.J. Richardson and Mr R.A. Daw. We thank the Science and Medical Research Councils, the British Diabetic Association and the Arthritis and Rheumatism Council for supporting our experimental work.     

Beeinflussung der Gerinnungswirkung von Heparin durch Serotonin und Tryptamin

Summary Investigations in the cofactor-fibrinogen system have shown that serotonin and tryptamine, although only in relatively high doses, reduce the antithrombin time prolonged by the action of heparin. Histamine has no such effect on the action of heparin, nor have tyramine and isoamylamine.

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Für wertvolle Ratschläge im Verlaufe der Untersuchungen sind wir den Herren Dr.R. Marbet, Dr.André Studer und PD Dr.A. Winterstein, Wissenschaftliche Laboratorien der F. Hoffmann-La Roche & Co. AG. in Basel zu Dank verpflichtet.