Stimulation of the synthesis and non-competitive inhibition of alkaline phosphatase by theophylline in normal hamster fibroblasts and absence of response in transformed fibroblasts]

Theophylline increases the synthesis of alkaline phosphatase in normal Hamster fibroblasts (activity X6 after 24 hours with theophylline 10-3 M). The enzymatic activity of these cells is inhibited by theophylline in vitro (80% inhibition in the presence of theophylline 10-3 M). The inhibition seems to be non competitive, since the apparent Km of the enzyme is not modified. This stimulator and inhibitor effect of theophylline is absent in Hamster fibroblasts transformed by SV 40 virus.     

Modification of theophylline-induced lipolysis in human fat cells after trypsination.

Trypsin-treatment of human fat cells results in the potentiation of the lipolytic response and the cAMP accumulation induced by theophylline (5 . 10(-4) M) but not of those induced by theophylline (5 . 10(-3) M). The amount of cAMP formed after exposure to theophylline (5 . 10(-3) M) plus norepinephrine (5 . 10(-6) M) remains, however, 2.6 fold higher in trypsin-treated human fat cells than in the control ones.     

Prolongation of the duration of motility and fertilizing ability of rainbow trout spermatozoa by the addition of theophylline to the dilution medium

After rainbow Trout sperm were diluted in 0.01 and 0.001 M theophylline media, motility and fertilizing ability were prolonged as compared to the control media without theophylline. However, the motility observed was lower and of a different type than normal motility. This suggests that other factors besides cyclic nucleotides intervene in the motility of Trout spermatozoa.     

Lack of effect of neurotransmitters on cyclic AMP phosphodiesterase activity in an insect CNS.

The inhibition of cyclic nucleotide phosphodiesterase from the nerve cord of Manduca sexta was studied using theophylline as a model compound. 11 putative neurotransmitters had no effect on enzyme activity.     

Effect of cyclic AMP and theophylline on phagocytotic activity of Tetrahymena pyriformis.

Dibutyril cAMP and the cPDE-inhibitor theophylline both enhance the phagocytotic activity of Tetrahymena. Theophylline and cAMP-activating histamine are synergistic. It follows that the cAMP-adenylcyclase system functions in the unicellular animal Tetrahymena.     

Ionic effects on cyclic nucleotide accumulation in a phytophagous insect

Summary Incubation in solutions containing high potassium levels reduces specific accumulation of cyclic AMP in larval nerve cords ofManduca, sexta in vitro with or without serotonin or theophylline.Supported in part by NIH grant NS-09161-20 to R.W.N.     

Effect of cyclic AMP and theophylline on phagocytotic activity ofTetrahymena pyriformis

Summary Dibutyril cAMP and the cPDE-inhibitor theophylline both enhance the phagocytotic activity ofTetrahymena. Theophylline and cAMP-activating histamine are synergistic. It follows that the cAMP-adenylcyclase system functions in the unicellular animalTetrahymena.     

Lack of effect of neurotransmitters on cyclic AMP phosphodiesterase activity in an insect CNS

Summary The inhibition of cyclic nucleotide phosphodiesterase from the nerve cord ofManduca sexta was studied using theophylline as a model compound. 11 putative neurotransmitters had no effect on enzyme activity.Supported in part by NIH grant NS-09161-20 to R. W. Newburgh     

Effects of gastric secretagogues on tissue glycerol in the isolated amphibian gastric mucosa

Histamine and theophylline, two gastric secretagogues, significantly increased tissue glycerol content by 121 and 66%, respectively, in the isolated toad gastric mucosa. This is new evidence in favor of the hypothesis that gastric secretagogues may act via lipid mobilization.     

Effect of dibutyryl cAMP and theophylline on cultured rat embryonic shields.

Effects of N6, O2 dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) and theophylline (Th) on cultured rat embryonic shields were studied. After addition of db-cAMP to the culture medium, an increase of the weight of explants and of the incidence of the skeletal muscle was observed. Theophylline seems to be ineffective.     

Die Wirkung von Theophyllin auf den cellulären Ca-Stoffwechsel des Warmblüterherzens

Summary In isolated, electrically driven, left guineapig atria, theophylline (5×10^–4 g/ml) increased the rate of⁴⁵Ca uptake and release without affecting the total myocardial Ca content and the amount of exchangeable cellular Ca. In sheep and calf heart preparations, theophylline (10^–4–10^–3 g/ml) increased Ca inward current during excitation (as examined indirectly by Ca dependent changes of membrane potential in TTX-containing solutions) as well as tension development. It is concluded that the positive inotropic effect of theophylline in mammalian hearts is due to an increase in Ca influx during the excitation process.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Modification of theophylline-induced lipolysis in human fat cells after trypsination

Summary Trypsin-treatment of human fat cells results in the potentiation of the lipolytic response and the cAMP accumulation induced by theophylline (5·10^–4 M) but not of those induced by theophylline (5·10^–3 M). The amount of cAMP formed after exposure to theophylline (5·10^–3 M) plus norepinephrine (5·10^–6 M) remains, however, 2.6fold higher in trypsin-treated human fat cells than in the control ones.Acknowledgments. The authors gratefully acknowledge the help of the surgical staff of the C. H. I. of Poissy. This work was supported by grants from the C. H. I. of Poissy and from the Université René Descartes.     

Studies on the activity of phorbol myrystate acetate on the human polymorphonuclear leukocytes.

Phorbol myrystate acetate (PMA) activates nitroblue tetrazolium reduction in human polymorphs. The activation is inhibited by dibutyryl cyclic AMP, theophylline and phenylbutazone, but is not influenced by hydrocortisone in vitro, nor is it inhibited by leukocytes from patients treated with prednisone. Peptide analogues of Tuftsin also had no effect on this stimulatory activity. We conclude that the action of PMA on the nitroblue tetrazolium reduction is mediated through cyclic nucleotides.     

Studies on the activity of phorbol myrystate acetate on the human polymorphonuclear leukocytes

Summary Phorbol myrystate acetate (PMA) activates nitroblue tetrazolium reduction in human polymorphs. The activation is inhibited by dibutyryl cyclic AMP, theophylline and phenylbutazone, but is not influenced by hydrocortisone in vitro, nor is it inhibited by leukocytes from patients treated with prednisone. Peptide analogues of Tuftsin also had no effect on this stimulatory activity. We conclude that the action of PMA on the nitroblue tetrazolium reduction is mediated through cyclic nucleotides.     

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).     

Effects of gastric secretagogues on tissue glycerol in the isolated amphibian gastric mucosa

Summary Histamine and theophylline, two gastric secretagogues, significantly increased tissue glycerol content by 121 and 66%, respectively, in the isolated toad gastric mucosa. This is new evidence in favor of the hypothesis that gastric segretagogues may act via lipid mobilization.This investigation was supported by Consejo de Desarrollo Científico y humanístico de la Universidad del Zulia, Maracaibo, Venezuela.     

Influence of cyclic nucleotides on protein synthesis in vascular smooth muscle.

The incorporation of leucine-14C into protein in bovine mesenteric arteries was augmented by cyclic GMP (10-3 M) and decreased by cyclic AMP (10-3 M). There was no effect of 5'AMP (10-3 M). The phosphodiesterase inhibiting drugs theophylline (10-3 M) and papaverine (5 x 10-5 g/ml) both decreased the leucine-14C incorporation.     

A negative inotropic effect of acetylcholine in the presence of several phosphodiesterase inhibitors

The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine (IBMX) reveal a negative inotropic effect of acetylcholine in cat ventricular heart muscle. This effect in unrelated to beta-adrenoceptor stimulation and possibly mediated by the accumulation of cyclic GMP.     

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

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.     

The reversal of glucose repressed prodigiosin production inSerratia marcescens by the cyclic 3′5′-adenosine monophosphate inhibitor theophylline

Summary Glucose was found to cause severe repression of prodigiosin production inSerratia marcescens and a dose related partial reversal was demonstrated by theophylline. It is suggested that this reversal is due to the inhibition of cAMP phosphodiesterase and the concomitant increase in cellular cAMP concentration.