Circling behavior induced by phencyclidine in mice and its inhibition by naloxone

Summary Phencyclidine (PCP), when given to mice, induces general hyperactivity and rapid circling, similar to that caused by morphine. These effects are partially antagonized by naloxone.Acknowledgment. We are grateful to Professor A. Kalir for the donation of PCP. Correspondence and reprint requests should be addressed to A. M. Korczyn.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

We investigated whether hypothalamic prostaglandin E2 (PGE2) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 alpha (IL-1 alpha). The present results show that ACTH responses induced by intravenous injection of IL-1 alpha were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE2 stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE2. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE2.     

Nitrite reduction by NADH, catalyzed by the nitrite reductase of Pseudomonas aeruginosa

Reduction of nitrite by NADH catalyzed by Pseudomonas aeruginosa nitrite reductase is inhibited by a high concentration of nitric oxide NO. Contrary to what is currently admitted, we find that the nitrite reduction proceeds to the nitrogen monoxide N2O stage. EPR spectra show that, during the catalytic cycle, the enzyme forms specific Fe2+-NO heminic complexes.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

Summary We investigated whether hypothalamic prostaglandin E₂ (PGE₂) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 (IL-1). The present results show that ACTH responses induced by intravenous injection of IL-1 were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE₂ stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE₂. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE₂.     

Modification by levo-propranolol of tremors induced by harmine in mice

Summary It has been recently reported that the levo isomer of propranolol possesses anti-serotonin properties in animals. Since harmine-induced behavioural changes in mice are reported to be mediated through central serotonergic receptors, an attempt was made to test whether 1-propranolol would also modify harmine-induced responses by virtue of its antiserotonergic or anti-adrenergic property. The results indicated that 1- and dl-propranolol inhibited central serotonin receptor mediated responses to harmine in mice, a finding that is analogous to other recent observations.     

Modification by levo-propranolol of tremors induced by harmine in mice

It has been recently reported that the levo isomer of propranolol possesses anti-serotonin properties in animals. Since harmine-induced behavioural changes in mice are reported to be mediated through central serotonergic receptors, an attempt was made to test whether 1-propranolol would also modify harmine-induced responses by virtue of its anti-serotonergic or anti-adrenergic property. The results indicated that l- and dl-propranolol inhibited central serotonin receptor mediated responses to harmine in mice, a finding that is analogous to other recent observations.     

Enhancement by caffeine of sister-chromatid exchange frequency induced by antineoplastic agents in human lymphocytes

Summary The SCE frequency induced by Thiotepa and the effect of this antineoplastic drug in combination with caffeine have been studied in cultures of human peripheral blood. Caffeine was found to enhance SCE and breakage frequencies induced by Thiotepa in human lymphocytes.Acknowledgment. I am deeply grateful to Dr M.J.W. Faed, for stimulating discussions, guidance and constructive criticism. This paper is a part of my Ph.D. thesis submitted to Dundee University.     

Urease inhibition by hydroxamic acids

Summary Ureases from jack beans andRhodototorula pilimanae were observed to be inhibited by primary hydroxamic acids but were not inhibited by acyclic-secondary (N-alkyl) hydroxamic acids.This project was supported by a Lamar University organized research grant.     

Degradation by phytohemagglutinin of the antiviral state induced by interferon]

Phytohaemagglutinin (PHA M and P forms), when added to L 929 cells previously treated by murine interferon, degrades the antiviral state and restores virus sensitivity in the cells. This degradation depends on the amount of the lectin, the contact period with the cell and the presence of PHA membrane receptors. The importance of membrane configuration not only in the induction but also in the maintenance of the antiviral state is discussed.     

Baroreceptor function changed by breathing

Summary The efferent sympathetic activity (ESA) of the carotid nerve is related to breathing, and can be driven by stimulation of the latter, e.g. by airway occlusion. The ESA controls both carotid wall stiffness and the excitability of nervous receptor elements. Therefore, breathing is capable of changing the carotid baroreceptor function.     

Recognition of apoptotic cells by phagocytes

Effective removal of dying cells is crucial to a variety of processes in health and disease. Cells undergoing apoptosis are recognized and ingested intact by phagocytes, which are not stimulated to release inflammatory mediators. The alternative uncontrolled form of cell death, necrosis, is associated with release of cell contents with the potential to cause tissue damage and inflammation. Four distinct molecular mechanisms have been identified to date which mediate recognition by phagocytes of mammalian cells undergoing apoptosis, but further mechanisms remain to be discovered. The capacity for phagocyte removal of cells undergoing apoptosis may be closely regulated, for example by local cytokines.     

Enhanced depressor reflex by stimulation of superior cervical ganglion and by propranolol

Summary The systemic depressor reflex in cats evoked by inflation of an intrasinusal balloon is enhanced by stimulation of the superior cervical ganglion and by close infusion of 20g/ml/min of (d, 1) propranolol.This work was supported by grant No. 22600-1 NIH, Heart, Lung and Blood Institute, Bethesda, MD.     

Inhibition of rat liver transglutaminase by nucleotides

Summary Tissue-type transglutaminase (TGase) was purified from rat liver, and the effects of nucleotides on its activity were examined. The enzyme activity is inhibited by ATP in a concentration-dependent way, with complete inhibition by 3 mM ATP. Partially-purified TGase from human brain was inhibited by ATP in a manner similar to that observed with the rat liver enzyme. This suggests that the inhibition is a common phenomenon for tissue-type TGase in all species and tissues. The inhibition is reversible since full activity is restored by lowering the ATP concentration. CTP has a TGase-inhibitory potency equivalent to that of ATP, whereas GTP and UTP possess about 50% of the inhibitory activity of ATP. ADP inhibits TGase activity to the same extent as ATP, but AMP causes much less inhibition, and there is no inhibition by adenosine or adenine. The inhibition by ATP is insensitive to ionic strength and is non-competitive with the substrate putrescine. Since ATP levels in cells are of mM order, these results suggest that TGase activity is controlled by ATP in vivo.     

Enhancement by caffeine of the frequency of anaphase-telophase chromatin bridges induced by triethylenemelamine (TEM)

Summary Treatment of BHK cells for 8 h with triethylenemelamine (TEM) followed by caffeine for 4 or 8 h, increased the frequency of anaphase-telophase chromatin bridges in relation to controls and TEM-treated cells. These results indicate that TEM-induced chromosome lesions detected as chromatin bridges at anaphase-telophase could be potentiated by caffeine.This work was supported by grants from CIC, CONICET and CAFPTA.     

Nuclear degeneration induced by chlortetracycline

Summary After application of chlortetracycline to plants, a degeneration of nuclei, manifested by dilatation and vacuolation of the nuclear membrane, occurs in the mesophyll cells of the sunflower plant.     

Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters

Cancer cell resistance to chemotherapy is often mediated by overexpression of P-glycoprotein, a plasma membrane ABC (ATP-binding cassette) transporter which extrudes cytotoxic drugs at the expense of ATP hydrolysis. P-glycoprotein (ABCB1, according to the human gene nomenclature committee) consists of two homologous halves each containing a transmembrane domain (TMD) involved in drug binding and efflux, and a cytosolic nucleotide-binding domain (NBD) involved in ATP binding and hydrolysis, with an overall (TMD-NBD)2 domain topology. Homologous ABC multidrug transporters, from the same ABCB family, are found in many species such as Plasmodiumfalciparum and Leishmania spp. protozoa, where they induce resistance to antiparasitic drugs. In yeasts, some ABC transporters involved in resistance to fungicides, such as Saccharomyces cerevisiae Pdr5p and Snq2p, display a different (NBD-TMD)2 domain topology and are classified in another family, ABCG. Much effort has been spent to modulate multidrug resistance in the different species by using specific inhibitors, but generally with little success due to additional cellular targets and/or extrusion of the potential inhibitors. This review shows that due to similarities in function and maybe in three-dimensional organization of the different transporters, common potential modulators have been found. An in vitro 'rational screening' was performed among the large flavonoid family using a four-step procedure: (i) direct binding to purified recombinant cytosolic NBD and/or full-length transporter, (ii) inhibition of ATP hydrolysis and energy-dependent drug interaction with transporter-enriched membranes, (iii) inhibition of cell transporter activity monitored by flow cytometry and (iv) chemosensitization of cell growth. The results indicate that prenylated flavonoids bind with high affinity, and strongly inhibit drug interaction and nucleotide hydrolysis. As such, they constitute promising potential modulators of multidrug resistance.     

Light-driven DNA repair by photolyases

DNA photolyases are highly efficient light-driven DNA repair enzymes which revert the genomedamaging effects caused by ultraviolet (UV) radiation. These enzymes occur in almost all living organisms exposed to sunlight, the only exception being placental mammals like humans and mice. Their catalytic mechanism employs the light-driven injection of an electron onto the DNA lesion to trigger the cleavage of cyclobutane- pyrimidine dimers or 6-4 photoproducts inside duplex DNA. Spectroscopic and structural analysis has recently yielded a concise view of how photolyases recognize these DNA lesions involving two neighboring bases, catalyze the repair reaction within a nanosecond and still achieve quantum efficiencies of close to one. Apart from these mechanistic aspects, the potential of DNA photolyases for the generation of highly UV-resistant organisms, or for skin cancer prevention by ectopical application is increasingly recognized. Received 29 September 2005; received after revision 30 November 2005; accepted 15 February 2006     

Enhancement by caffeine of sister-chromatid exchange frequency induced by antineoplastic agents in human lymphocytes.

The SCE frequency induced by Thiotepa and the effect of this antineoplastic drug in combination with caffeine have been studied in cultures of human peripheral blood. Caffeine was found to enchance SCE and breakage frequencies induced by Thiotepa in human lymphocytes.     

Control of energy homeostasis by amylin

Amylin is an important control of nutrient fluxes because it reduces energy intake, modulates nutrient utilization by inhibiting postprandial glucagon secretion, and increases energy disposal by preventing compensatory decreases of energy expenditure in weight-reduced individuals. The best investigated function of amylin which is cosecreted with insulin is to reduce eating by promoting meal-ending satiation. This effect is thought to be mediated by a stimulation of specific amylin receptors in the area postrema. Secondary brain sites to mediate amylin action include the nucleus of the solitary tract and the lateral parabrachial nucleus, which convey the neural signal to the lateral hypothalamic area and other hypothalamic nuclei. Amylin may also signal adiposity because plasma levels of amylin are increased in adiposity and because higher amylin concentrations in the brain result in reduced body weight gain and adiposity, while amylin receptor antagonists increase body adiposity. The central mechanisms involved in amylin's effect on energy expenditure are much less known. A series of recent experiments in animals and humans indicate that amylin is a promising option for anti-obesity therapy especially in combination with other hormones. The most extensive dataset is available for the combination therapy of amylin and leptin. Ongoing research focuses on the mechanisms of these interactions.