Inhibitory effects of spermine and spermidine on muscle calpain II

Summary The muscle enzyme calpain II, in contrast to muscle calpain I, was markedly inhibited by millimolar concentrations of the polyamines spermine and spermidine. These compounds and the calpain inhibitor calpastatin had synergistic inhibitory effects on calpain II. These results suggest that the polyamines may have possible regulatory effects on the in vivo activity of calpain II enzymes.     

Development of new hypoxic cell sensitizers: Amides of nitrobenzoic acid with spermidine and spermine

Summary New type hypoxic cell sensitizers, N¹, N¹⁰-bis(4-nitrobenzoyl)spermidine (1) and N¹,N¹⁴-bis(4-nitrobenzoyl)-spermine (2), have been developed. These compounds were shown to be more effective radiosensitizers to hypoxic cells than misonidazole (3).     

Effects of receptor agonists on polyamine concentrations and spermidine/spermine N1-acetyltransferase activity in rat parotid gland

The polyamine putrescine might be formed via a degradation (catalyzed by spermidine/spermine N¹-acetyltransferase, SSAT) of the higher polyamines spermidine and spermine to putrescine. The involvement of different intracellular signal pathways in the regulation of putrescine formation was studied in explants and in cultured cells of rat parotid glands by using receptor agonists that activate separate second messenger systems, and measuring their effects on the concentrations of putrescine, spermidine and spermine and on the SSAT activity. The -adrenoceptor agonist isoprenaline, which is an activator of cAMP formation, increased the putrescine concentration and stimulated the SSAT activity. Pilocarpine, a drug that activates the muscarinic receptors and thereby enhances the phosphoinositide turnover, had no effect on either the polyamine concentrations or on the SSAT activity. Epidermal growth factor (EGF), which induces activation of a protein tyrosine kinase, had no effect on the polyamine concentrations or on the SSAT activity. The adenylate cyclase activator forskolin increased the glandular levels of putrescine. Taken together, these findings suggest that increases in putrescine concentration in cultured rat parotid gland cells are accompanied by accumulation of cAMP.     

Inhibitory effects of flavonoids on several venom hyaluronidases

In vitro studies showed that the flavonoid aglycones apigenin, luteolin and kaempferol inhibited the hyaluronidase activity of five different venoms dose-dependently. They were also able to delay the venom action when injected into mice. Naringenin, catechin and flavonoid glycosides had no effect. The flavonoids with unsubstituted hydroxyl groups at C-positions 5, 7 and 4′, a double bond between carbons 2 and 3, as well as a ketone group at position 4, exhibited potent inhibitory actions on the venom hyaluronidases.     

Inhibitory effects of flavonoids on several venom hyaluronidases.

In vitro studies showed that the flavonoid aglycones apigenin, luteolin and kaempferol inhibited the hyaluronidase activity of five different venoms dose-dependently. They were also able to delay the venom action when injected into mice. Naringenin, catechin and flavonoid glycosides had no effect. The flavonoids with unsubstituted hydroxyl groups at C-positions 5, 7 and 4', a double bond between carbons 2 and 3, as well as a ketone group at position 4, exhibited potent inhibitory actions on the venom hyaluronidases.     

Inhibitory effects of LHRH on ovarian LH receptors in rats]

The administration of LHRH or of its analog [D-Ala6, des-Gly-NH10(2)] LHRH ethylamide to the female rat on day 10 of gestation resulted in termination of pregnancy and in a marked decrease in ovarian LH receptors and plasma progesterone level. Asingle injection of either compound during diestrus I also led to a decrease in LH receptors. These data demonstrate the high sensitivity of the control of ovarian LH receptors by circulating gonadotrophins and suggest that the contraceptive action of pre- and postcoitally administered LHRH is mediated by negative control of LH receptors.     

Inhibitory effects of nitrososarcosine on mouse liver mixed function oxidase activity

Zusammenfassung Nachweis, dass Nitrosarcosin im Gegensatz zu Dimethyl- und Dibutylnitrosamin die nichtfunktionelle Oxidase in der Mäuseleber hemmt.

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This work was supported by N.I.E.H.S. grant No. ES 00713.

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We are indebted to the technical help of Ms.Heather McClanahan.     

Fusimotor effects on position and velocity sensitivity of muscle spindles

Zusammenfassung Primäre und sekundäre Muskelspindelendigungen der Katze wurden mit sowie ohne statische und dynamische -Aktivierung, bei periodischer Dehnung und Entspannung über einen weiten Geschwindigkeitsbereich untersucht. Es wurde die Lage- und Geschwindigkeitsempfindlichkeit bestimmt; dabei wurden 2 Typen statischer -Effekte bei den primären wie auch sekundären Endigungen beobachtet.

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This work was supported by the Swedish Medical Research Council (Project No. 14X-544-02), and by Karolinska Institutet (Reservationsanslaget för främjande av ograduerade forskares vetenskapliga verksamhet).     

Denervation effects on choline depolarization of muscle membrane

Résumé Dans un muscle non dénervé, la choline provoque une dépolarisation permanente en présence de «Cs-Ringer» et transitoire en présence de «K-Ringer». La dénervation augmente la sensibilité de la membrane musculaire à la choline. Mais dans ce cas, le «Cs-Ringer» donne une réponse transitoire à la choline, semblable à celle obtenue avec le «K-Ringer».     

Inhibitory action ofγ-aminobutyric acid (GABA) onAscaris muscle

Zusammenfassung Die somatische Muskulatur vonAscaris lumbricoides wird durch-Aminobuttersäure in Konzentrationen von 10^–6-10^–5 M völlig gehemmt. Eine hnliche Hemmung wird durch Piperazin (10^–3 M) erzielt. Beide Substanzen steigern die Cl-Permeabilität der Muskelmembran.

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On leave of absence from the Instituto de Biofísica, Universidade do Brazil, Rio de Janeiro (Brazil).     

Inhibitory effects of phenolic compounds on CCl4-induced microsomal lipid peroxidation

The antiperoxidative effects of 35 phenolic compounds, most of them belonging to the flavonoid class, were investigated using CCl4-induced peroxidation of rat liver microsomes. This system was rather insensitive to gallic acid, methyl gallate and ellagic acid. Nevertheless it was inhibited by flavonoids and structure/activity relationships were established. The most potent compounds were gardenin D, luteolin, apigenin (flavones), datiscetin, morin, galangin (flavonols), eriodictyol (flavanone), amentoflavone (biflavone) and the reference compound, (+)-catechin. The natural polymethoxyflavone gardenin D has shown a potency comparable to that of (+)-catechin and higher than that of silybin. Thus, it may be considered as a new type of natural antioxidant with potential therapeutical applications.     

Inhibitory effects of LHRH on LH receptors in the rat testis]

A single injection of LHRH to the adult male rat, as of its analog [D-Ala6, des-Gly-NH102] LHRH ethylamide, resulted in a marked decrease in LH receptors in the tests. Plasma testosterone level and the weight of the seminal vesicles and prostate were also decreased after treatment. These data demonstrate that LHRH can decrease the sensitivity of LH receptors and testicular function in the rat.     

Inhibitory effects of phenolic compounds on CCl4-induced microsomal lipid peroxidation

Summary The antiperoxidative effects of 35 phenolic compounds, most of them belonging to the flavonoid class, were investigated using CCl₄-induced peroxidation of rat liver microsomes. This system was rather insensitive to gallic acid, methyl gallate and ellagic acid. Nevertheless it was inhibited by flavonoids and structure/activity relationships were established. The most potent compounds were gardenin D, luteolin, apigenin (flavones), datiscetin, morin, galangin (flavonols), eriodictyol (flavanone), amentoflavone (biflavone) and the reference compound, (+)-catechin. The natural polymethoxyflavone gardenin D has shown a potency comparable to that of (+)-catechin and higher than that of silybin. Thus, it may be considered as a new type of natural antioxidant with potential therapeutical applications.     

Effect of spermine on adenyl cyclase activity of spermatozoa

Zusammenfassung Zusätze physiologischer Sperminkonzentrationen (2–14 mM) zu menschlichen Spermiensuspensionen bewirken eine Steigerung der Adenylcyclase-Aktivität, wie sie durch die vermehrte Bildung von cAMP aus ATP angezeigt wird.     

Sodium concentration and the effect of angiotensin II on iieal smooth muscle

Zusammenfassung Die kontraktile Reaktion des isolierten Meerschweinchen-Ileums auf Angiotensin II variierte direkt mit der Natriumkonzentration der Nährflüssigkeit, nicht aber bei ACh; Atropin (10^–6 g/ml) reduzierte die Wirkung auf Angiotensin um 60–70% und hob die Wirkung auf äquivalente Mengen von ACh auf. In atropinhaltiger Ringerlösung potenzierte ein hoher Natriumgehalt (+ 30 meq./l) die Reaktion auf Angiotensin zehnfach.     

Pleiotropic effects of sonic hedgehog on muscle satellite cells

Muscle satellite cells are believed to form a stable, self-renewing pool of stem cells in adult muscle where they function in tissue growth and repair. A regulatory disruption of growth and differentiation of these cells is assumed to result in tumor formation. Here we provide for the first time evidence that sonic hedgehog (Shh) regulates the cell fate of adult muscle satellite cells in mammals. Shh promotes cell division of satellite cells (and of the related model C2C12 cells) and prevents their differentiation into multinucleated myotubes. In addition, Shh inhibits caspase-3 activation and apoptosis induced by serum deprivation. These effects of Shh are reversed by simultaneous administration of cyclopamine, a specific inhibitor of the Shh pathway. Taken together, Shh acts as a proliferation and survival factor of satellite cells in the adult muscle. Our results support the hypothesis of the rhabdomyosarcoma origin from satellite cells and suggest a role for Shh in this process.Received 23 February 2005; received after revision 2 May 2005; accepted 9 June 2005