Increase of interferon antiviral activity by exogenous cyclic adenosine-3′∶5′-monophosphate (cAMP)

Summary Some effects of cAMP on replication of Semliki Forest Virus in chick embryo fibroblast cell cultures are described. Depending on concentration, the incorporation of [³H]-uridine into viral RNA or the formation of plaqueforming units is inhibited; the highest concentration tested was 8 mM. Cyclic AMP has an effect of its own and increases the Interferon action in the lower concentration ranges of Interferon (up to 1 unit/ml). The effect of cyclic AMP is fast, needs no induction and is also visible in late phases of viral replication. However, these experiments do not establish a causal relation between cAMP and Interferon.Work supported by the Swiss National Science Foundation, grants 3.1050 and 3.540.     

Measurement of cyclic AMP in the islets of Langerhans of newborn rats. Effect of amino acids]

Radioimmunoassay of cyclic AMP (cAMP) in the islets of Langerhans from 48-64 h old Rats was performed after succinylation of the samples. cAMP was detected at 0.03 nM. The cAMP content of islets increases when L-arginine, L-lysine and L alanine are added together in the incubation medium at a concentration of 5-10 mM each. When phosphodiesterase is inhibited by theophylline the three amino acids considerably increase the cAMP content of islets. Thus an increase in cAMP content of the islets was observed with a concentration of amino acids which is efficient in stimulating the insulin and glucagon secretion.     

Effect of dibutyryl cyclic AMP and analogs on the rate of contractions of myocytes in culture.

2O, 6N-butyryl, 3', 5'-cyclic monophosphate (dibu cAMP) when added to fetal rat heart cells in culture inhibits myocyte contraction. This inhibition is 100, 84 and 51% complete when the dibu cAMP concentration used is 2, 0.2 and 0.02 mM, respectively. The potency of dibu cAMP derivatives in myocyte contraction inhibition follows the order, dibu cAMP greater than 6N-bu cAMP greater than 2O-bu cAMP = AMP greater than butyrate. The inhibition caused by the first three chemicals is greater than 70%.     

The role of cyclic adenosine monophosphate in the swarming phenomenon of Proteus mirabilis.

The levels of cylic AMP and adenyl cyclase in swarming and non-swarming cells of Proteus mirabilis and the effect of glucose on swarming have been investigated. The results indicate the cAMP is required for swarming, but that the flagellar derepression characteristic of swarming does not result from increased cAMP levels.     

The role of cyclic adenosine monophosphate in the swarming phenomenon ofProteus mirabilis

Summary The levels of cyclic AMP and adenyl cyclase in swarming and non-swarming cells ofProteus mirabilis and the effect of glucose on swarming have been investigated. The results indicate that cAMP is required for swarming, but that the flagellar derepression characteristic of swarming does not result from increased cAMP levels.One of the authors (JPA) thanks the S.R.C. for financial support.     

Inhibition of virus multiplication and alteration of cyclic AMP level in cell cultures by flavonoids

The inhibitory effect of four flavonoid compounds on virus multiplication and their influence on the intracellular cyclic AMP (cAMP) level were studied in cell cultures. Quercetin and quercitrin reduced the yields of Human (alpha) herpesvirus 1 (HSV-1) and Suid (alpha) herpesvirus 1 (pseudorabies virus), but hesperidin and rutin had no effect. Further, quercetin and quercitrin elevated the intracellular level of cAMP, whereas hesperidin and rutin did not alter the cAMP level. Both antiviral activity and cAMP-enhancing effect were dependent on the concentrations of the flavonoids, and these effects turned out to be parallel. This study suggests that a relation exists between the antiviral effect and the cAMP-enhancing activity of flavonoids.     

Inhibition of virus multiplication and alteration of cyclic AMP level in cell cultures by flavonoids

Summary The inhibitory effect of four flavonoid compounds on virus multiplication and their influence on the intracellular cyclic AMP (cAMP) level were studied in cell cultures. Quercetin and quercitrin reduced the yields ofHuman (alpha) herpesvirus 1 (HSV-1) andSuid (alpha) herpesvirus 1 (pseudorabies virus), but hesperidin and rutin had no effect. Further, quercetin and quercitrin elevated the intracellular level of cAMP, whereas hesperidin and rutin did not alter the cAMP level. Both antiviral activity and cAMP-enhancing effect were dependent on the concentrations of the flavonoids, and these effects turned out to be parallel.This study suggests that a relation exists between the antiviral effect and the cAMP-enhancing activity of flavonoids.     

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

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.     

Effects of several preoperative medications on fat cell lipolysis, and activity of adipose tissue cyclic AMP phosphodiesterase.

Effects were examined of atropine, diazepam, pethidene, promethazine, scopolamine, omnopon and papaverine on basal and noradrenaline-stimulated lipolysis in rat isolated fat cells and on rat adipose tissue cyclic AMP phosphodiesterase activity. Papaverine at high concentration (1 mM) inhibited both basal and hormone-stimulated lipolysis, whereas diazepam enhanced basal lipolysis. At a 'clinical dose', omnopon increased both basal and noradrenaline-stimulated lipolysis. Adipose tissue cAMP phosphodiesterase activity was strongly inhibited by 1 mM diazepam, papaverine, promethazine and omnopon (280 microgram ml-1). Lack of enhancement of lipolysis by the established cAMP phosphodiesterase antagonist papaverine, is compatible with simultaneous inhibition also of adipose adenyl cyclase. Diazepam-stimulated lipolysis is compatible with its phosphodiesterase inhibitory activity. It is proposed that papaverine-containing omnopon may offer some survival advantages during surgical stress by facilitating a caloric supply.     

Intracellular cyclic AMP in vesicular stomatitis or Senda? virus infected cells (author's transl)

In KB cells, MRC5 and adult skin fibroblasts infected by low doses of Senda? virus, intracellular cyclic AMP levels rose and fell in the first hours following infection, then remained lower than basal level during at least 2 days in KB cells and adult skin fibroblasts. When compared to other viruses or cAMP inducers previously described, this effect appeared specific of Senda? virus. Mechanisms and roles of cAMP variations are discussed. VSV-infected KB cells showed slightly decreased cAMP levels during the first hours following infection.     

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.     

The brachymorphic mutation of mice and altered developmental patterns of limb bud 3':5' cyclic adenosine monophosphate

Concentrations of cyclic AMP (cAMP) were determined in paired fore and hind limbs from day 12-16 of development in murine fetuses homozygous for the brachymorphic (bm) mutation and normal controls. A developmental rise in cAMP occurred 1 day earlier in bm/bm than in +/+ hind limbs and cAMP was higher in day-13 bm/bm than in +/+ fore limbs. Since cAMP is well documented to stimulate chondrogenic differentiation, premature cartilage determination secondary to altered levels of cAMP could play a role in bm/bm short-limbed dwarfism.     

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.     

Prostaglandin-like substances in Propionibacterium acnes II. Stimulatory effect on ovarian cyclic AMP.

The prostaglandin-like substances (PLS) from Propionibacterium acnes increased the ovarian tissue levels of cyclic AMP (cAMP) approximately 2-fold. The lipid material extracted from P. acnes thus behaved like PG's of the E-type, and since it is unlikely that other known stimulators of the ovarian cAMP system can be present in the bacterial lipid fraction, these experiments give further evidence in favour of the occurrence of PLS in P. acnes.     

The brachymorphic mutation of mice and altered developmental patterns of limb bud 3′∶5′ cyclic adenosine monosphosphate

Summary Concentrations of cyclic AMP (cAMP) were determined in paired fore and hind limbs from day 12–16 of development in murine fetuses homozygous for the brachymorphic (bm) mutation and normal controls. A developmental rise in cAMP occurred 1 day earlier inbm/bm than in +/+ hind limbs and cAMP was higher in day-13bm/bm than in +/+ fore limbs. Since cAMP is well documented to stimulate chondrogenic differentiation, premature cartilage determination secondary to altered levels of cAMP could play a role inbm/bm short-limbed dwarfism.This work was supported by a grant from the National Foundation-March of Dimes.     

Prostaglandin-like substances inPropionibacterium acnes II. Stimulatory effect on ovarian cyclic AMP

Summary The prostaglandin-like substances (PLS) fromPropionibacterium acnes increased the ovarian tissue levels of cyclic AMP (cAMP) approximately 2-fold. The lipid material extracted fromP. acnes thus behaved like PG's of the E-type, and since it is unlikely that other known stimulators of the ovarian cAMP system can be present in the bacterial lipid fraction, these experiments give further evidence in favour of the occurrence of PLS inP. acnes.