Adenosine 3',5'-monophosphate is localized in cerebellar neurons: immunofluorescence evidence

Adenosine 3',5'-monophosphate is localized in specific cerebellar neurons, as shown by fluorescence immunocytochemistry with a specific rabbit immunoglobulin. Positive staining is exhibited by Purkinje neurons and granule cells. The increase in concentration of cyclic adenosine monophosphate in the cerebellum, which is known to follow decapitation, is represented by greatly increased fluorescence of Purkinje neurons only. These immunofluorescence data provide the first evidence for localization of cyclic adenosine monophosphate in specific neurons and may permit further exploration into the role of this cyclic nucleotide in neuronal function.     

Guanosine 3',5'-monophosphate in sympathetic ganglia: increase assoicated with synaptic transmission

Brief stimulation of cholinergic preganglionic nerve fibers resulted in an increase in guanosine 3',5'-monophosphate (cyclic GMP) in the bullfrog sympathetic ganglion. When the release of synaptic transmitter was prevented by a high-magnesium, low-calcium Ringer solution, stimulation of preganglionic nerve fibers did not increase cyclic GMP in the ganglion. The increase in cyclic GMP caused by preganglionic stimulation was also blocked by the muscarinic antagonist, atropine. The data indicate that the increase in cyclic GMP is associated with synaptic transmission and support the possibility that cyclic GMP may mediate the postsynaptic action of acetylcholine at muscarinic cholinergic synapses.     

Adenosine 3'5'-monophosphate phosphodiesterase: multiple molecular forms

By starch-gel electrophoresis and a specific staining technique, seven different molecular forms of cyclic nucleotide phosphodiesterase have been demonstrated in supernatants from homogenates of rat and rabbit tissues. No tissue contains more than four components, but there are distinct differences in component patterns among the various tissues. Tentative molecular weights of the three most prevalent components of rat tissues have been estimated at 135,000, 150,000, and 167,000 by sucrose density gradient centrifugation.     

Adenosine 3',5'-monophosphate in pancreatic islets: glucose-induced insulin release

Glucose-induced release of insulin from perifused rat islets is associated with elevated islet adenosine 3',5'-monophosphate. If values for adenosine 3',5'-monophosphate are compared to insulin release during theophylline or glucose stimulation and theophylline plus glucose stimulation, it suggests a minor role for adenosine 3',5'-monophosphate in directly stimulating insulin release but a prominent role in modulating glucose-induced release of insulin.     

Adenosine 3'5'-monophosphate: inhibition of complement-mediated cell lysis

An increase in adenosine 3',5'-monophosphate (cyclic AMP) in rat mast cells, achieved by stimulating the cells with prostaglandin E(1), by preventing cyclic AMP breakdown with aminophylline, or by adding exogenous dibutyryl cyclic AMP, prevented complement-mediated cytolysis as assessed by both histamine release and vital dye exclusion. Dibutyryl cyclic AMP also suppressed water-induced osmotic lysis.     

Adenosine 3',5'-monophosphate waves in Dictyostelium discoideum: a demonstration by isotope dilution--fluorography

The distribution of adenosine 3',5'-monophosphate (cyclic AMP) in fields of aggregating amoebae of Dictyostelium discoideum was examined by a novel isotope dilution-fluorographic technique. Cellular cyclic AMP was visualized by its competition with exogenous 3H-labeled cyclic AMP for high-affinity binding sites on protein kinase immobilized on a Millipore filter used to blot the monolayer. The cyclic AMP was distributed in spiral or concentric circular wave patterns which centered on the foci of the aggregations. These patterns were correlated with those of cell shape change that propagate through the monolayers: cells in regions of high concentrations of cyclic AMP were elongated (presumably moving up a cyclic AMP gradient), whereas those in regions of low cyclic AMP concentrations were randomly directed. The highest cyclic AMP concentrations were about 10(-6)M. The widths of the regions of elevated cyclic AMP were about 0.3 to 1 millimeter which, assuming a wave velocity of 300 micrometers per minute, suggests that a cell signals for about 1 to 3 minutes. These observations support the hypothesis that the aggregation process in Dictyostelium is mediated by the periodic relay of cyclic AMP signals and suggest a simple scheme for the dynamics of the aggregation process.     

Adenosine 3',5'-monophosphate phosphodiesterase in the growth medium of Physarum polycephalum

The acellular slime mold Physarum polycephalum releases a soluble adenosine 3', 5'-monophosphate phosphodiesterase into the growth medium. Although this enzyme resembles the particulate diesterase of the same organism in kinetic properties and in inhibition by methyl purines, its greater stability, its insensitivity to stimulation by imidazole and to inhibition by adenosine triphosphate,- and its selective release into the medium indicate a specific function, perhaps protection against exogenous cyclic nucleotide, for the soluble enzyme.     

Adenosine 3',5'-monophosphate, adrenocorticotropic hormone, and adrenocortical cytosol protein synthesis

In cultures of mouse adrenocortical tumor cells (Sato's minimal deviation Y-1 clonal strain), the acceleration of steroid biosynthesis after exposure to adrenocorticotropic hormone or cyclic adenosine 3',5'-monophosphate is maximum within 15 to 60 minutes and precedes any significant increase in labeling of protein with [4,5-(3)H]leucine. However, when cytosol proteins are separated by acrylamidegel electrophoresis, rapid changes in the amount and labeling of several protein fractions are evident in less than 30 minutes and are no longer evident within 60 minutes. This finding supports the proposal that the effects of tropic hormones and their intracellular mediators involve rapid selective effects on protein synthesis.     

Adenosine 3',5'-monophosphate modulates thyrotropin receptor clustering and thyrotropin activity in culture

A biologically active rhodamine conjugate of thyrotropin binds at 4 degrees C to diffusely distributed membrane thyrotropin receptors which patch and become endocytosed into thyroid cells in a temperature-sensitive process. When the cells are first incubated with 8-bromo-cyclic adenosine monophosphate at 37 degrees C, the conjugate also binds to clustered receptors at 4 degrees C. Furthermore, 8-bromo-cyclic adenosine monophosphate reduces the amount of adenosine 3',5'-monophosphate (cyclic AMP) induced by thyrotropin. Hence, increased intracellular cyclic AMP induces receptor patching and reduces the concentration of cyclic AMP normally induced by thyrotropin. This suggests that cyclic AMP acts both as the second messenger of thyrotropin and also as the regulator of the level of thyrotropin receptors.     

Adenosine 3',5'-monophosphate: regional differences in chick embryos at the head process stage

The concentrations of adenosine 3',5'-monophosphate and adenosine triphosphate and the activity of phosphodiesterase were determined in different regions of chick embryos at the head process stage. Adenosine 3',5'-monophosphate, adenosine triphosphate, and phosphodiesterase were estimated to be higher in the mesoderm-forming portions of the hypoblast than in portions that form neural structures from Hensen's node or the epiblast.     

Adenosine 3',5'-monophosphate content in rat caudate nucleus: demonstration of dopaminergic and adrenergic receptors

Dopamine, apomorphine, isoproterenol, and norepinephrine each increased the concentration of adenosine 3',5'-monophosphate in slice of rat caudate nucleus. The concentrations of dopamine, apomorphine isoproterenol, and norepinephrine causing half-maximal increases were 60, 150, 0.03 and 30 micromoles per liter, respectively. The effect of dopamine was blocked by fluphenazine, a dopamine receptor antagonist, but not by propranolol, a beta-andrenergic receptor antagonist. Conversely, the effect of isoproterenol was blocked by propranolol but not by fluphenazine. The results suggest that in rat caudate nucleus there are two distinct catecholamine receptors capable of causing increased concentrations of adenosine 3',5'-monophosphate, one having the characteristic of dopamine receptor, and the other having the characteristics of beta-adrenergic receptor.     

Histone phosphorylation: stimulation by adenosine 3',5'-monophosphate

Adenosine cyclic 3',5'-monophosphate at a concentration of 10-(7)M causes a four-to sixfold increase in the rate of histone phosphorylation catalyzed by a liver enzyme preparation. This observation suggests a mechanism for the induction of RNA synthesis by those hormones that cause increases in the concentration of cyclic AMP.     

Melatonin synthesis: adenosine 3',5'-monophosphate and norepinephrine stimulate N-acetyltransferase

Treatment of cultured rat pineal glands with norepinephrine or dibutyryl adenosine 3',5'-monophosphate causes a six- to tenfold stimulation of N-acetyltransferase. This enzyme converts serotonin to N-acetylserotonin, the immediate precursor of melatonin. The increased synthesis of melatonin caused by norepinephrine treatment appears to be the result of stimulation of N-acetyltransferase by an adenosine 3',5'-monophosphate mechanism.     

Tyrosine aminotransferase: enzyme induction independent of adenosine 3', 5'-monophosphate

The importance of adenyl cyclase and adenosine 3',5'-monophosphate in the induction of tyrosine aminotransferase by adrenocorticosteroids has been tested in HTC cells derived from a rat hepatoma and grown in tissue culture. Adrenocorticosteroids cause a 10-to 15-fold increase in the rate of synthesis of tyrosine aminotransferase in these cells. Under various experimental conditions, with or without glucocorticoids, neither adenyl cyclase nor cyclic adenosine mono-phosphate could be detected in HTC cells. In addition, neither the cyclic nucleotide nor N(6), O(2')-dibutyryl cyclic adenosine monophosphate caused increased activity of the transaminase in HTC cells. We conclude that induction of tyrosine aminotransferase by glucocorticoids is not mediated by the adenyl cyclase-cyclic adenosine monophosphate system.     

Adenosine 3',5'-monophosphate-dependent protein kinase from brain

Adenosine 3',5'-monophosphate at a concentration of 5 x 10(-7) mole per liter causes a 400 percent increase in the rate of phosphorylation of histone catalyzed by a partially purified enzyme preparation from rabbit brain. The data provide the first direct evidence of a biochemical action of adenosine 3',5'-monophosphate in the brain.     

Gonadotropin-releasing hormone: regulation of adenosine 3',5'-monophosphate in ovarian granulosa cells

The antigonadal effects of gonadotropin-releasing hormone in ovarian granulosa cells are due to attenuation of the adenosine 3',5'-monophosphate (cyclic AMP) response to follicle-stimulating hormone. Agonists of gonadotropin-releasing hormone progressively inhibit adenylate cyclase and stimulate phosphodiesterase activities in cultured granulosa cells, indicating that blockade of gonadotropin action is attributable to the combined effects of decreased production and increased degradation of cyclic AMP.     

Inhibition of cell growth in vitro by adenosine 3',5'-monophosphate

Adenosine 3',5'-monophosphate, at a concentration of 40 micrograms per milliliter, inhibits the growth of HeLa and strain L cells in culture. The inhibition becomes progressively greater during the incubation of the cells. Adenosine 5'-monophosphate and adenosine, metabolites of adenosine 3',5'-monophosphate, do not affect the growth of either cell culture. This suggests that 3',5'-monophosphate enters the cell without alteration. Dibutyryl-adenosine 3',5'-monophosphate, reported to have a greater activity than adenosine 3'5'-monophosphate on several tissues, inhibited the growth of the cells much less.     

Adenosine 3'-5'-monophosphate in rat pineal gland: increase induced by light

Rats were maintained in alternating periods of 12 hours of light and 12 hours of darkness. The concentration of adenosine 3',5'-monophosphate in pineal gland was six times higher at the end of the light period than at the end of the period of darkness. This effect of light was abolished in blinded animals.