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.     

Hormone and forskolin-stimulated cyclic AMP accumulation in human lymphocytes: reliability of longitudinal time measurements

Reliability of measurement of lymphocyte cyclic AMP synthesis in intact cells was estimated by taking 3 successive blood samples during a one-month period from 11 healthy volunteers. Isoproterenol and prostaglandin E1-stimulated cyclic AMP accumulation were used to evaluate the activity of these two receptor activities in human lymphocytes. Forskolin-stimulated cyclic AMP accumulation was used to evaluate the activity of the Ns/catalytic subunit. Only for forskolin was significant reliability observed. For isoproterenol and prostaglandin E1 significant reliability was observed only for male subjects.     

Hormone and forskolin-stimulated cyclic AMP accumulation in human lymphocytes: reliability of longitudinal time measurements

Summary Reliability of measurement of lymphocyte cyclic AMP synthesis in intact cells was estimated by taking 3 successive blood samples during a one-month period from 11 healthy volunteers. Isoproterenol and prostaglandin E₁-stimulated cyclic AMP accumulation were used to evaluate the activity of these two receptor activities in human lymphocytes. Forskolin-stimulated cyclic AMP accumulation was used to evaluate the activity of the Ns/catalytic subunit. Only for forskolin was significant reliability observed. For isoproterenol and prostaglandin E₁ significant reliability was observed only for male subjects.Acknowledgment. This work was supported in part by the following organizations: Chief Scientist's Office, Israel Ministry of Health; Herman Goldman Foundation, New York; United Jewish Endowment Fund of Greater Washington-Pollinger Foundation.     

Inhibition of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary by alrestatin

Summary Alrestatin at 25–1×10^–4 M inhibited the accumulation of cyclic AMP induced by prostaglandin E₂, but not theophylline, in the rat anterior pituitary in vitro. Somatostatin, at lower concentrations, inhibited both; maximal inhibition of the prostaglandin effect was greater with alrestatin. As cyclic AMP is considered to be a mediator in induced-hormonal release, it appears from the present findings that alrestatin may be of potential use in altering hormonal release.The author acknowledges the technical assistance of Miss C. Pilapil.     

Pineal-related changes in cyclic AMP levels of rat medial basal hypothalamus

Summary Pinealectomy (Px) in adult male rats resulted in increased cyclic AMP accumulation by medial basal hypothalamic (MBH) explants 3 and 7 days after surgery. 24 h after superior cervical ganglionectomy (Gx) an augmented MBH cyclic AMP accumulation was observed. The effects of Px and Gx were additive, as revealed in animals subjected to Gx 3 days after Px.This study was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (N^o 6638) and from the Fundación Alberto J. Roemmers, Argentina.     

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.     

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).     

Altered brain cyclic AMP-responses in rats reared in enriched or impoverished environments

Summary The accumulation of radioactive cyclic AMP elicited by various neurohormones has been examined in adenine-labeled telencephalon slices from rats raised in enriched or impoverished environments. Basal levels of cyclic AMP and responses of the brain slice cyclic AMP-generating systems to norepinephrine, isoproterenol and adenosine did not differe between the two group of rats, while responses to prostaglandin E₁ were significantly greater with the impoverished group and responses to histamine appeared to be greater with the enriched group.     

Inhibition of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary by alrestatin.

Alrestatin at 25-1 X 10(-4) M inhibited the accumulation of cyclic AMP induced by prostaglandin E2, but not theophylline, in the rat anterior pituitary in vitro. Somatostatin, at lower concentrations, inhibited both; maximal inhibition of the prostaglandin effect was greater with alrestatin. As cyclic AMP is considered to be a mediator in induced-hormonal release, it appears from the present findings that alrestatin may be of potential use in altering hormonal release.     

Role of adenosine A1 and A2 receptors in the regulation of aldosterone production in rat adrenal glands

Summary To investigate the roles of adenosine A₁ and A₂ receptors in the regulation of aldosterone production, we examined the effects of adenosine and adenosine agonists (N⁶-cyclohexyl adenosine; selective adenosine A₁ receptor agonist and 5-N-ethylcarboxamine adenosine; selective adenosine A₂ receptor agonist) on aldosterone and cyclic AMP production in rat adrenal capsular cells. Neither adenosine nor 5-N-ethylcarboxamine adenosine caused significant effects on basal aldosterone or cyclic AMP production. Also, adenosine (10^–3M) showed no consistent effects on aldosterone and cyclic AMP production induced by ACTH. On the other hand, N⁶-cyclohexyl adenosine exhibited a significant inhibition of basal aldosterone and cyclic AMP production at doses of 10^–4 M and 10^–3 M; furthermore, 10^–3 M N⁶-cyclohexyl adenosine inhibited aldosterone and cyclic AMP production stimulated by ACTH. These results suggest that adenosine A₁ receptors are coupled to and inhibit adenylate cyclase and may be involved in the inhibition of aldosterone production.     

Altered brain cyclic AMP-responses in rats reared in enriched or impoverished environments.

The accumulation of radioactive cyclic AMP elicited by various neurohormones has been examined in adenine-labeled telencephalon slices from rats raised in enriched or impoverished environments. Basal levels of cyclic AMP and responses of the brain slice cyclic AMP-generating systems to norepinephrine, isoproterenol and adenosine did not differ between the two group of rats, while responses to prostaglandin E1 were significantly greater with the impoverished group and responses to histamine appeared to be greater with the enriched group.     

Cyclic AMP accumulation in human fibroblast cultures: diabetics compared with normals

Isoproterenol-stimulated accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in skin fibroblast cultures from type 2 diabetics was twice as high as in fibroblasts from control subjects.     

Antithyroid effect of a food or drug preservative: 4-hydroxybenzoic acid methyl ester

Summary 4-hydroxybenzoic acid methyl ester (methylparaben) inhibits organification of iodide by isolated hog thyroid cells. The concentration which produces a 50% inhibition was about 2.0×10^–4M. A similar inhibition was observed in nonstimulated and TSH- or dibutyryl cyclic AMP-stimulated cells. Neither iodide uptake nor cyclic AMP generation were altered by methylparaben.     

Antagonism of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary in vitro by somatostatin analogues

Summary The PGE₂-induced cyclic AMP accumulation in the rat anterior pituitary in vitro is inhibited by [desamino¹]-, [desamino¹] [descarboxy¹⁴] and [d-Lys⁴]-somatostatin similarly to somatostatin, while the [descarboxy¹⁴]-somatostatin exhibits reduced activity; [d-Lys⁹]-somatostatin is ineffective at a higher concentration.The authors acknowledge the technical assistance ofG. Alexander. F. Bellini, D. Mangerel andJ. Rochon and thank Dr.G. Schilling and his associates for the analytical data.     

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.     

Suppression of chaos by periodic oscillations in a model for cyclic AMP signalling inDictyostelium cells

We investigate how the introduction of cells oscillating periodically affects the behaviour of a suspension ofDictyostelium discoideum amoebae undergoing chaotic oscillations of cyclic AMP. The analysis of a model indicates that a tiny proportion of periodic cells suffices to transform chaos into periodic oscillations in such suspensions. A similar result is obtained by forcing the aperiodic oscillations by a small-amplitude, periodic input of cyclic AMP. The results provide an explanation for the observation of regular oscillations in suspensions of a putatively chaotic mutant ofDictyostelium discoideum ¹². More generally, the results show how chaos in biological systems may disappear through the coupling with periodic oscillations.     

Influence of cyclic nucleotides on protein synthesis in vascular smooth muscle

Summary The incorporation of leucice-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 (5×10^–5 g/ml) both decreased the leucine-¹⁴C incorporation.We are indebted to Mrs.Lena Burlin for hear assistance. Finacial support has been provided by the Swedish State Medical Research Council (No. 04X-101X-4498).     

The effect of cyclic AMP on Na+ and K+ transport systems in mouse macrophages

Summary Exogenous cyclic AMP (cAMP) inhibits the Na⁺, K⁺-cotransport system and stimulates the Na⁺, K⁺-pump and Na⁺, Ca²⁺ exchange in mouse macrophages. These effects are enhanced by inhibition of phosphodiesterase with methylisobutylxanthine (MIX). MIX alone showed little or no effect. A similar response was observed after stimulation of endogenous production of cAMP by isoproterenol.     

Stimulation of H+ ion secretion from the isolated mouse stomach by sodium fluoride

Summary The effect of sodium fluoride on H⁺ ion secretion was investigated in the isolated distended mouse stomach. It was found that sodium fluoride on its own caused dose-related stimulation of H⁺ ion secretion. Sodium fluoride did not inhibit H⁺ ion secretion induced by histamine. The possible mechanisms involved are discussed. It is considered that sodium fluoride might stimulate H⁺ ion secretion by causing histamine release and by increasing cyclic AMP formation in the intact gastric mucosa.     

Stimulation of ribonuclease activity and its isoenzymes in germinating seeds of cowpea (Vigna sinensis) by gibberellic acid and adenosine-3′,5′-cyclic monophosphate

Summary Application of GA₃ and cyclic AMP to cowpea seedlings caused a 2–3 fold stimulation of RNAase activity, together with the augmentation of RNAase isoenzymes. Inhibitor studies indicated the requirement of fresh RNA and protein synthesis for enzyme stimulation.