Adenosine 3',5'-monophosphate: electrophysiological evidence for a role in synaptic transmission

Synaptic potentials and changes in resting membrane potentials of superior cervical ganglia of the rabbit were measured in the presence of adenosine 3',5'-monophosphate and agents that affect its metabolism. Adenosine 3',5'-monophosphate and its mono- and dibutyryl derivatives caused a hyperpolarization of the postganglionic neurons. Theophylline potentiated the slow inhibitory postsynaptic potential that follows synaptic transmission, as well as the hyperpolarization of postganglionic neurons caused by exogenous dopamine. Conversely, prostaglandin E(1) inhibited both the slow inhibitory postsynaptic potential and the dopamine-induced hyperpolarization. We hypothesize that the slow inhibitory postsynaptic potential as well as the dopamine-induced hyperpolarization result from increased amounts of adenosine 3'5'-monophosphate in the postganglionic neurons. The dibutyryl derivative of guanosine 3'5'-monophosphate caused a depolarization of the postganglionic neurons, which is consistent with the possibility that guanosine 3'5'-monophosphate mediates synaptic transmission at muscarinic cholinergic synapses.     

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-dependent protein kinase of cultured mammalian cells

Protein kinase was partially purified from Chang's liver cells, 3T6 mouse embryo fibroblasts, and HeLa cells. The rate of histone phosphorylation catalyzed by the kinase from each of these cell lines was stimulated two- to three-fold by 1 x 10(-6) molar adenosine 3',5'-monophosphate. The same concentration of guanosine 3',5'-monophosphate failed to stimulate these kinases.     

Cyclic guanosine and adenosine 3',5'-monophosphates in canine thyroid: localization by immunofluorescence

When guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) are localized in canine thyroid by a flurescence Immunocytochemical procedure, distinct staining patterns for each nucleotide are seen: Cyclic AMP is distributed throughout the follicular cell cytoplasm before and after administration of thyroid-stimulating hormone, while cyclic GMP is localized to the follicular cell mumbrane in the control state, and increased cytoplasmic fluorescence is visualized after acetylcholine. These data provide histological evidence that correlates with cyclic nucleotide tissue measurements, sugesting diverse roles of the two nucleotides in thyroid function.     

Cyclic adenosine monophosphate stimulation of axonal elongation

Elevated concentrations of adenosine 3',5'-monophosphate induce a variety of cell movements. The role of adenosine 3',5'-monophosphate in promoting those movements associated with growth prompted our study of in vitro microtubule-dependent axonal elongation. Ganglia treated with adenosine 5'-monophosphate show no enhancement over controls; treatment with adenosine 3', 5'monophosphate or its dibutyryl derivative significantly enhances elongation, as measured by increases in both axonal numbers and length. Our study suggests that adenosine 3',5'-monophosphate promotes elongation by stimulation of microtubule assembly.     

Fluorescent modification of adenosine 3',5'-monophosphate: spectroscopic properties and activity in enzyme systems

The synthesis of a highly fluorescent analog of adenosine 3',5'-monophosphate, namely, 1,N(6)-ethenoadenosine 3',5'-monophosphate, has provided a powerful probe for systems involving adenosine 3',5'-monophosphate. The potential utility of this analog is indicated by its long fluorescent lifetime, detectability at low concentration, and relatively long wavelength of excitation (300 nanometers). In protein kinase systems it is a highly acceptable substitute for adenosine 3',5'-monophosphate.     

Hormonal control of neutrophil lysosomal enzyme release: effect of epinephrine on adenosine 3',5'-monophosphate

Human neutrophilic leukocytes release neutral protease and beta-glucuronidase during cell contact with, and phagocytosis of, zymosan particles treated with rheumatoid arthritic serum. Release of lysosomal enzymes is inhibited by epinephrine and adenosine 3',5'-monophosphate (cyclic AMP), but not by phenylephrine or adenosine 5'-monophosphate. Inhibition of enzyme release by epinephrine may be mediated by cyclic AMP because the cyclic AMP in the neutrophils is increased by epinephrine treatment at the time when enzyme release is reduced.     

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.     

Divergent biological effects of adenosine and dibutyryl adenosine 3',5'-monophosphate on the isolated fat cell

Adenosine 3',5'-monophosphate stimulated production of carbon dioxide and lipid from glucose, whereas its dibutyryl derivative inhibited this conversion. Addition of the dibutyryl derivative to the isolated fat cell further stimulated lipolysis induced by adrenocorticotropic hormone, whereas addition of adenosine 3',5'-monophosphate inhibited this lipolysis. Hence, measured by these two parameters, the biologic properties of adenosine 3',5'-monophosphate and its dibutyryl derivative are distinctly different.     

Histamine augments leukocyte adenosine 3',5'-monophosphate and blocks antigenic histamine release

Extracellular histamine stimulates accumulation of adenosine 3',5'-monophosphate in human leukocytes and prevents antigenic release of histamine from cells of allergic donors. Both effects occur at histamine concentrations that can be achieved by antigenic release of the amine in vitro.     

Vasoactive intestinal peptide alters membrane potential and cyclic nucleotide levels in retinal horizontal cells

Vasoactive intestinal peptide stimulated the synthesis of adenosine 3',5'-monophosphate in fractions of isolated carp horizontal cells. When applied extracellularly to isolated and cultured horizontal cells, the peptide also induced a slow depolarization (30 to 40 millivolts) accompanied by a decrease in membrane resistance. However, analogs of adenosine 3',5'-monophosphate applied extracellularly or intracellularly, and forscolin applied extracellularly, had no effect on the membrane potential of cultured horizontal cells, indicating that the induced depolarization was not related to the accumulation of adenosine 3',5'-monophosphate in these cells.     

Nerve growth factor: relationship to the cyclic AMP system of sensory ganglia

Nerve growth factor and N(6),O(2)' dibutyryl adenosine 3',5'-monophosphate both stimulate neurite elongation by explanted ganglia. However, the addition of nerve growth factor does not lead to increased amounts of adenosine 3',5'-monophosphate in intact ganglia, nor does it stimulate adenylate cyclase activity in broken ganglia cells.     

Cell growth with trans fatty acids is affected by adenosine 3',5'-monophosphate and membrane fluidity

Two positional isomers (9 and 11) of trans octadecenoates did not support growth on glucose of an Escherichia coli mutant that requires unsaturated fatty acids. However, the trans fatty acids provided sufficient fluidity to produce much higher cell yields when the concentration of adenosine 3',5'-monophosphate was raised. The effectiveness of the trans acids rose from 0 to 1 cell per femtomole to 15 to 20 cells per femtomole as the concentration of adenosine 3',5'-monophosphate was increased. The corresponding cis positional isomers supported high yields (35 to 40 cells per femtomole) independent of supplementation. The enhanced growth with adenosine 3',5'-monophosphate supplementation is not due to an increased uptake and incorporation of the trans isomers relative to the cis isomers, since the 9-trans isomer was incorporated more rapidly than the 9-cis isomer into the membrane phospholipids under all growth conditions and represented 21 +/- 2 mole percent of the acids. The finding that cells growing with trans fatty acid isomers have a higher requirement for adenosine 3',5'-monophosphate may indicate that some fatty acids can alter the metabolic regulation normally exerted by the cyclic nucleotide.     

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.     

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 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-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.     

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.     

Effects of dibutyryl cyclic AMP on restoration of function of damaged sciatic nerve in rats

In two experiments, the sciatic nerve of rats was either crushed or hemisected, and N(6),O(2)-dibutyryl adenosine 3',5'-monophosphate or saline was injected intramuscularly near the site of the lesion. In both types of nerve damage, the sensorimotor functions of animals treated with N(6),O(2)-dibutyryl adenosine 3',5'-monophosphate returned earlier than did those of saline-treated control animals.