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.     

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.     

Regional cyclic AMP levels in homogenates of rat brain after ketalar and trifluoperazine

There was a significant fall in cAMP levels after administration of TFP or ketalar. Different amounts of cAMP were present in different regions of rat brain. Concentrations of cAMP in different regions of the rat brain were found to decrease in the following order: cerebrum > thalamus with hypothalamus > midbrain > hippocampus > cerebral cortex.     

Regional cyclic AMP levels in homogenates of rat brain after ketalar and trifluoperazine

Summary There was a significant fall in cAMP levels after administration of TFP or ketalar. Different amounts of cAMP were present in different regions of rat brain. Concentrations of cAMP in different regions of the rat brain were found to decrease in the following order: cerebrum > thalamus with hypothalamus > midbrain > hippocampus > cerebral cortex.Conducted under ocntract No 10.4.2 with the Polish Academy of Science.     

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.     

Effects of adenohypophysectomy on cAMP levels in chick embryo thyroid,adrenal and spleen

Summary cAMP levels in thyroid and adrenal are higher in 17-day-old decapitated chick embryos than in controls, while spleen cAMP is not modified.This work was supported by a grant from D. G. R. S. T.     

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.     

The inhibitory effect of paraquat on histamine and isoproterenol induced changes of cyclic nucleotides in rat lung slices.

The incubation of rat lung slices with paraquat ion (10(-4) M) had no effect on cAMP and cGMP levels of the rat lung slices. The preincubation with the same concentration of paraquat inhibited the cAMP elevating effect of histamine (10(-5) M) and isoproterenol (10(-5) M) and reduced the cGMP level to approximately 50% of the level obtained without preincubation with paraquat.     

Alterations in the levels of cAMP and cGMP after decentralization of the rat superior cervical ganglion

Summary After cutting the preganglionic nerve trunk of the rat's superior cervical ganglion, the levels of cAMP and cGMP were measured in a postoperative period of between 3 and 21 days. After 3 days, cAMP and cGMP showed a decrease by 48 and 33% respectively, followed by a partial recovery after 7 to 21 days.This work was supported by the Deutsche Forschungsgemeinschaft (SFB 70).     

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.     

Regional and strain variation in brain 3′∶5′ cyclic adenosine monophosphate of inbred mice

Summary Regional variations were found in cAMP levels in flash frozen mouse brains with the pons and cerebellum having higher levels than the cerebrum. There were also strain variations with CBA/J and BALB/cJ having higher levels than C57B1/6J in the pons and cerebellum.     

Regional and strain variation in brain 3':5' cyclic adenosine monophosphate of inbred mice.

Regional variations were found in cAMP levels in flash frozen mouse brains with the pons and cerebellum having higher levels than the cerebrum. There were also strain variations with CBA/J and BALB/cJ having higher levels than C57B1/6J in the pons and cerebellum.     

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.     

Alterations in the levels of cAMP and cGMP after decentralization of the rat superior cervical ganglion.

After cutting the preganglionic nerve trunk of the rat's superior cervical ganglion, the levels of cAMP and cGMP were measured in a postoperative period of between 3 and 21 dad by a partial recovery after 7 to 21 days.     

Rosette formation by human T and B lymphocytes in the presence of adrenergic and cholinergic drugs.

It was shown that adrenergic drugs, which increase the intracellular levels of cAMP, inhibit the rosette formation by T-lymphocytes, but stimulate the rosettes produced by B-lymphocytes. Cholinergic drugs, which increase the levels of cGMP, on the contrary, stimulate the formation of rosettes by T-lymphocytes but inhibit those produced by B-lymphocytes.     

Impact of atypical mitochondrial cyclic-AMP level in nephropathic cystinosis

Nephropathic cystinosis (NC) is a rare disease caused by mutations in the CTNS gene encoding for cystinosin, a lysosomal transmembrane cystine/H⁺ symporter, which promotes the efflux of cystine from lysosomes to cytosol. NC is the most frequent cause of Fanconi syndrome (FS) in young children, the molecular basis of which is not well established. Proximal tubular cells have very high metabolic rate due to the active transport of many solutes. Not surprisingly, mitochondrial disorders are often characterized by FS. A similar mechanism may also apply to NC. Because cAMP has regulatory properties on mitochondrial function, we have analyzed cAMP levels and mitochondrial targets in CTNS^?/? conditionally immortalized proximal tubular epithelial cells (ciPTEC) carrying the classical homozygous 57-kb deletion (delCTNS^?/?) or with compound heterozygous loss-of-function mutations (mutCTNS^?/?). Compared to wild-type cells, cystinotic cells had significantly lower mitochondrial cAMP levels (delCTNS^?/? ciPTEC by 56%?±?10.5, P?<?0.0001; mutCTNS^?/? by 26%?±?4.3, P?<?0.001), complex I and V activities, mitochondrial membrane potential, and SIRT3 protein levels, which were associated with increased mitochondrial fragmentation. Reduction of complex I and V activities was associated with lower expression of part of their subunits. Treatment with the non-hydrolysable cAMP analog 8-Br-cAMP restored mitochondrial potential and corrected mitochondria morphology. Treatment with cysteamine, which reduces the intra-lysosomal cystine, was able to restore mitochondrial cAMP levels, as well as most other abnormal mitochondrial findings. These observations were validated in CTNS-silenced HK-2 cells, indicating a pivotal role of mitochondrial cAMP in the proximal tubular dysfunction observed in NC.     

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%.     

Transduction of the chemotactic cAMP signal across the plasma membrane ofDictyostelium cells

AggregatingDictyostelium cells secrete cAMP during cell aggregation. cAMP induces two fast responses, the production of more cAMP (relay) and directed cell locomotion (chemotaxis). Extracellular cAMP binds to G-protein-coupled receptors leading to the activation of second messenger pathways, including the activation of adenylyl cyclase, guanylyl cyclase, phospholipase C and the opening of plasma membrane Ca²⁺ channels. Many genes encoding these sensory transduction proteins have been cloned and null mutants of nearly all components have been characterized in detail. Undoubtedly, activation of adenylyl cyclase is the most complex, involving G-proteins, a soluble protein called CRAC and components of the MAP kinase pathway. Null mutants in this pathway do not aggregate, but can exhibit chemotaxis and develop normally when supplied with exogenous cAMP. The pathways leading to the activation of phospholipase C were identified, but unexpectedly, deletion of the phospholipase C gene has no effect on chemotaxis and development, nor on intracellular Ins(1,4,5)P₃ levels; the metabolism of this second messenger will be discussed in some detail. Activation of guanylyl cyclase is G-protein-dependent and essential for chemotaxis. Analysis of a collection of chemotactic mutants reveals that most mutants are defective in either the production or intracellular detection of cGMP, thereby placing this second messenger at the center of chemotactic signal transduction. Analysis of the cAMP-mediated opening of plasma membrane calcium channels in signal transduction mutants suggests that it has two components, one that depends on G-proteins and intracellular cGMP and one that is G-protein-independent.     

Epidermal growth factor stimulates proliferation of rat hepatoma cells producing alpha-fetoprotein.

Epidermal growth factor stimulated both [3H]thymidine uptake and proliferation of rat AH66 hepatoma cells. However, the increase in cell number was not accompanied by a proportional increase in the levels of alpha-fetoprotein of the culture media. The effects of EGF on the cell proliferation were antagonized by N6,O2'-dibutyryl cAMP.     

The inhibitory effect of paraquat on histamine and isoproterenol induced changes of cyclic nucleotides in rat lung slices

Summary The incubation of rat lung slices with paraquat ion (10^–4 M) had no effect on cAMP and cGMP levels of the rat lung slices. The preincubation with the same concentration of paraquat inhibited the cAMP elevating effect of histamine (10^–5 M) and isoproterenol (10^–5 M) and reduced the cGMP level to approximately 50% of the level obtained without preincubation with paraquat.This work was supported by the Research Grant No. 5 R01 HL 19720-03 from NHLI Department of Health, Education and Welfare, Washington, D.C.