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.     

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.     

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.     

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.     

Enzyme release from polymorphonuclear leukocyte lysosomes: regulation by autonomic drugs and cyclic nucleotides

Osmotic release of beta-glucuronidase from polymorphonuclear leukocyte lysosomes is inhibited by catecholamines and adenosine 3',5'-monophosphate, and accelerated by cholinergic agents and guanosine 3',5'-monophosphate. These actions are specific for the sympathetic and parasympathetic neurotransmitters and for the two cyclic nucleotides, as phenylephrine, tyramine, choline, adenosine 5'-monophosphate and guanosine 5'-monophosphate do not inodify lysosomal enzyme release.     

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.     

Dibutyryl cyclic adenosine monophosphate stimulation of colcemid-inhibited axonal elongation

Adenosine 3',5'-monophosphate (cyclic AMP) and its dibutyryl derivative induce a variety of morphological changes, including those associated with in vitro axonal maturation. Established sensory ganglia treated with dibutyryl cyclic AMP show significant increases in average axonal length and number in comparison with controls; those treated with maintenance doses of Colcemid show no increases in either parameter; simultaneous treatment with both agents results in growth statistically similar to that produced by dibutyryl cyclic AMP alone. The data are consistent with our hypothesis that cyclic AMP promotes axonal elongation by stimulating microtubule assembly from a preexisting subunit pool.     

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.     

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.     

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.     

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.     

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-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.     

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.     

Involvement of adenosine 3',5'-monophosphate in the activation of tyrosine hydroxylase elicited by drugs

Immediately after the injection of reserpine (16 micromoles per kilogram, intraperitoneally), aminophylline (200 micromoles per kilogram, intraperitoneally), and carbamylcholine (8.2 micromoles per kilogram, intraperitoneally), the concentration of adenosine 3',5'-monophosphate in adrenal medulla of rats is increased severalfold. The three drugs also cause a delayed increase of medullary tyrosine hydroxylase activity. Our results are consistent with the view that an increase of medullary adenosine 3',5'-monophosphate concentration is involved in the drug-induced increase of tyrosine hydroxylase activity in adrenal medulla. Experiments with tyramine (130 micromoles per kilogram, intraperitoneally) suggest that the increase of tyrosine hydroxylase activity and of adenosine 3',5'-monophosphate concentrations is independent of an increase in adrenal catecholamine turnover rate.     

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.     

Dopamine-sensitive adenyl cyclase: possible role in synaptic transmission

An adenyl cyclase activated by low concentrations of dopamine has been found in the mammalian superior cervical sympathetic ganglion. The existence of this enzyme may account for the increased amount of adenosine 3',5' monophosphate associated with synaptic activity in the ganglion. The results suggest that the physiological effects of dopamine in the ganglion, and possibly elsewhere in the nervous system, may be mediated by stimulating the synthesis of 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.     

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.