Effect of sodium butyrate in combination with prostaglandin E1 and inhibitors of cyclic nucleotide phosphodiesterase on human amelanotic melanoma cells in culture.

Sodium butyrate and cyclic AMP-stimulating agents (prostaglandin E1, papaverine, theophylline, and RO20-1724) caused reductions in the cell number (primarily due to reduction in cell division) when added individually to human melanoma cells in culture. However, the combination of sodium butyrate with one of the cyclic AMP-stimulating agents produced a marked reduction in cell number (primarily due to cell death).     

Effect of sodium butyrate in combination with X0irradiation,chemotherapeutic and cyclic AMP stimulating agents on neuroblastoma cells in culture

Summary Sodium butyrate, X-irradiation, chemotherapeutic agents and cyclic AMP-stimulating agents caused reduction in the cell number (due to cell death and reduction in cell division) when added individually to mouse neuroblastoma cells in culture. However, the combination of sodium butyrate with X-irradiation, chemotherapeutic and cyclic AMP-stimulating agents produced a greater reduction in the cell number than that produced by the individual agents.     

Effect of sodium butyrate in combination with X-irradiation, chemotherapeutic and cyclic AMP stimulating agents on neuroblastoma cells in culture.

Sodium butyrate, X-irradiation, chemotherapeutic agents and cyclic AMP-stimulating agents cuased reduction in the cell number (due to cell death and reduction in cell division) when added individually to mouse neuroblastoma cells in culture. However, the combination of sodium butyrate with X-irradiation, chemotherapeutic and cyclic AMP-stimulating agents produced a greater reduction in the cell number than that produced by the individual agents.     

Beta-adrenergic-stimulated adenylate cyclase activity in normal and EBV-transformed lymphocytes

Summary Beta-adrenergic-associated cyclic AMP accumulation was studied in intact lymphocytes before and after transformation with Epstein-Barr virus into immortal cell lines. Although a marked reduction in isoproterenol-stimulated cyclic AMP synthesis was observed in transformed cells, forskolin-stimulated cyclic AMP accumulation was preserved. A parallel loss of¹²⁵-iodocyanopindolol binding sites suggests that the reduction in beta-adrenergic-stimulated AMP synthesis is due to receptor down regulation.     

Monolayer cultures of normal adult rat adrenocortical cells: Steroidogenic responses to nucleotides,bacterial toxins and antimicrotubular agents

Summary Monolayer cultures of normal rat adrenocortical cells were treated with agents which stimulate steroidogenesis by Y-1 adrenal tumour cells. Choleragen was active, whereas cyclic nucleotides other than cyclic AMP, bacterial endotoxins and antimicrotubular agents were inactive.This work was supported by the Medical Research Council of Great Britain (grant No. 970/656/B). I am grateful to MissR. Magee for technical assistance and Prof.A. M. Neville for continued support.     

Beta-adrenergic-stimulated adenylate cyclase activity in normal and EBV-transformed lymphocytes

Beta-adrenergic-associated cyclic AMP accumulation was studied in intact lymphocytes before and after transformation with Epstein-Barr virus into immortal cell lines. Although a marked reduction in isoproterenol-stimulated cyclic AMP synthesis was observed in transformed cells, forskolin-stimulated cyclic AMP accumulation was preserved. A parallel loss of 125-iodocyanopindolol binding sites suggests that the reduction in beta-adrenergic-stimulated AMP synthesis is due to receptor down-regulation.     

Effect of various solubilizers on angiotensinII receptors in bovine adrenocortical plasma membranes

Summary 3 monionic detergents, Triton X-100, Lubrol WX and NP-40, inhibited binding of [³H]-AT_II to bovine adrenocortical plasma membranes. This effect appeared to be direct and not due to solubilization of the AT_II receptor by these agents. Sodium deoxycholate and the chaotropic ions, ClO ₄ ^– and Br^–, produced effects similar to the nonionic detergents.Supported by grants from the Quebec Heart Foundation and the Medical Research Council of Canada. The authors acknowledge the technical assistance of Mrs D. Michaud and the secretarial aide of Mrs D. Huot-Blais, and Miss L. Leblanc.     

A comparison of 3 reagents in converting thiamine to thiochrome in the presence of plant extracts and polyphenols

Summary Assays of thiamine added to plant extracts, known polyphenols and reducing agents, using K₃Fe(CN)₆, HgCl₂ and CNBr showed that the CNBr method was the least susceptible to redox interference and gave the highest thiochrome yield.Acknowledgments. We thank the International Foundation for Science, Sweden, and the National Research Council of Thailand for financial support.     

Niche width of parasites in species-rich and species-poor communities

Summary Niche width of ectoparasites of marine fishes, as measured by host range and microhabitat width, is not affected by the number of species in a community. There is no reduction in species numbers of Monogenea due to greater numbers of other parasite species, and frequencies of infection with Monogenea are greater in tropical, species-rich communities.Supported by grants from the Australian Research Grants Committee and the University of New England. M. Heap provided valuable technical assistance, and F. Roubal made his data onAcanthopagrus australis available to me.     

Adenosine promoted accumulation of adenosine 3′,5′-monophosphate in rabbit vagus nerve

Summary Desheathed rabbit vagus nerve has been found to form cyclic AMP when incubated with adenosine. This accumulation of cyclic AMP is inhibited by theophylline but not by antiadrenergic agents, anticholinergic agents or local anaesthetics. Depolarizing media are not able to promote cyclic AMP accumulation in this preparation.Acknowledgment. We gratefully acknowledge Mr.G. Jones for valuable discussion, MrsM. Moosmayer and Mr.S. Ferrara for expert technical assistance and Swiss National Science Foundation for grant support (Nr. 3.478.0.75).     

Effect of prostaglandins and dibutyryl cyclic AMP on the morphology of cells in primary astroglial cultures and on metabolic enzymes of GABA and glutamate metabolism

Summary Prostaglandins (PGE₁) and dibutyryl cyclic AMP (dBc AMP) induce similar morphological changes in astrocytes obtained in primary cultures. PGE₁ and dBc AMP increased 2 enzymes of GABA and glutamate metabolism, GABA-T and AAT, but did not modify GDH and GLN-S. Prostaglandins probably affect the cAMP content of glial cells and act in the same way as dBc AMP on glial cell differentiation.     

Effect of human serum on alkaline phosphatase induction in cultured human tumor cells

The continuous cell lines T 24 and HT-29, derived from human bladder and colon carcinomas, produce term-placental and intestinal alkaline phosphatase, respectively. Growth in hyperosmolar medium or exposure to prednisolone or sodium butyrate induces increased enzyme levels, and combinations of inducers elicit synergistic activity increases. The effect of the inducing agents is strikingly diminished when cells are grown in the presence of high concentrations of human serum, and the synergistic increases are essentially abolished. Major human serum protein fractions do not affect alkaline phosphatase induction.     

Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia

Summary Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N₂, 12% O₂ and 4% CO₂. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p<0.01) and a decrease in cyclic GMP (p<0.05) as compared to hearts perfused for 60 min with media gassed with 96% O₂, 4% CO₂.Acknowledgment. We gratefully acknowledge the excellent technical assistance provided by Mrs Inger O. Boggs and Miss Patricia C. Hannigan. This work was supported in part by U. S. Public Health Service grant HL 14661 from the National Heart and Lung Institute, and by a grant from the Central Ohio Heart Chapter.     

Allergic reactions,cyclic AMP and histamine release

Summary Both isobutylmethylxantine and theophylline increased the level of cyclic AMP in the mast cell. Theophylline reduced the allergic histamine release, whereas isobutylmethylxynthine caused a pronounced potentiation of the histamine release. This indicates that the hypothesis of an inverse relationship between the level of cyclic AMP in mast cells and histamine release is too simple.This work was supported by grants from the Danish Medical Research Council (Grant No. 512-5270) and from Lundbeckfonden.     

Quantitative cytophotometric analyses of mesenteric mast cell granulation in acute soman intoxicated rats

Summary Effects of the organophosphate neurotoxin soman on rat mesenteric mast cell granule content were determined using scanning-integrating microdensitometric analysis of individual cell metachromasia. Mast cell degranulation was evidenced both with sublethal (0.5 LD₅₀) and lethal (1.5 LD₅₀) dosages and as early as 3–10 min post-injection. These data indicate a possible contribution of mast cell autacoids in the genesis of organophosphate-induced respiratory and circulatory collapse.Supported by U.S. Army Medical Research and Development Command Contract DAMD-17-81-C-1202.     

The behavior of alloxan in the Hill reaction

Summary Hill activity induced by alloxan is characterized by non-stoichiometric oxygen evolution and cyclic electron flow due to autoxidation of dialuric acid and alloxantin, the reduction products of alloxan.     

The oxygen consumption of some tissues from hypophysectomized goldfish,Carassius auratus L.

Summary Hypophysectomy has no effect on the O₂ consumption of minced brain and white muscle tissue, while liver tissue shows a marked reduction. This reduction in liver O₂ consumption is attributed to the increased glycogen content that follows hypophysectomy which has the effect of increasing the nonmetabolizing dry weight component of the cells.Supported by the National Research Council of Canada, Grant Number A-3744 to P. H. J.     

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle

Vascular smooth muscle tone is controlled by a balance between the cellular signaling pathways that mediate the generation of force (vasoconstriction) and release of force (vasodilation). The initiation of force is associated with increases in intracellular calcium concentrations, activation of myosin light-chain kinase, increases in the phosphorylation of the regulatory myosin light chains, and actin-myosin crossbridge cycling. There are, however, several signaling pathways modulating Ca²⁺ mobilization and Ca²⁺ sensitivity of the contractile machinery that secondarily regulate the contractile response of vascular smooth muscle to receptor agonists. Among these regulatory mechanisms involved in the physiological regulation of vascular tone are the cyclic nucleotides (cAMP and cGMP), which are considered the main messengers that mediate vasodilation under physiological conditions. At least four distinct mechanisms are currently thought to be involved in the vasodilator effect of cyclic nucleotides and their dependent protein kinases: (1) the decrease in cytosolic calcium concentration ([Ca²⁺]c), (2) the hyperpolarization of the smooth muscle cell membrane potential, (3) the reduction in the sensitivity of the contractile machinery by decreasing the [Ca²⁺]c sensitivity of myosin light-chain phosphorylation, and (4) the reduction in the sensitivity of the contractile machinery by uncoupling contraction from myosin light-chain phosphorylation. This review focuses on each of these mechanisms involved in cyclic nucleotide-dependent relaxation of vascular smooth muscle under physiological conditions.     

The rate of action of cyclic ammonium and sulfonium analogues of acetylcholine

Summary The rate of action of cyclic acetylcholine analogues in the 4-acetoxypiperidine and 4-acetoxythiacyclohexane series has been determined by using the isolated left guinea-pig atrium. The kinetic data obtained has been correlated with the experimental ED₅₀-value on the muscarinic receptor.Structure and Conformation Activity Relationships of Cyclic Acetylcholine Analogues.VI.We thank the German Research Association for supporting this work, and Mrs Ch. Röttger for her valuable assistance in carrying out the investigations.     

Effect of human serum on alkaline phosphatase induction in cultured human tumor cells

Summary The continuous cell lines T 24 and HT-29, derived from human bladder and colon carcinomas, produce term-placental and intestinal alkaline phosphatase, respectively. Growth in hyperosmolar medium or exposure to prednisolone or sodium butyrate induces increased enzyme levels, and combinations of inducers elicit synergistic activity increases. The effect of the inducing agents is strikingly diminished when cells are grown in the presence, of high concentrations of human serum, and the synergistic increases are essentially abolished. Major human serum protein fractions do not affect alkaline phosphatase induction.