Pineal gland: dibutyryl cyclic adenosine monophosphate stimulation of labeled melatonin production

In organ cultures of intact rat pineal glands, N(6)O(2')-dibutyryl adenosine 3', 5'-monophosphate stimulates the conversion of tritiated trytophan to tritiated melatonin, as does L-norepinephrine. Potential sites of stimulation of melatonin production by dibutyryl cyclic adenosine monophosphate are discussed, based on observations that the dibutyryl analog also stimulates the conversion of serotonin labeled with carbon-14 to carbon-14-labeled melatonin without altering hydroxyin-dole-O-methyl transferase activity or intracellular accumulation of serotonin labeled with carbon-14.     

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.     

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.     

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.     

In vivo inhibition of growth of two hormone-dependent mammary tumors by dibutyryl cyclic AMP

Growth of hormone-dependent rat mammary tumors was arrested in vivo by N(6),O(2)'-dibutyryl cyclic adenosine 3',5'-monophosphate. Estrogen concentration did not change, but acid ribonuclease activity and synthesis increased during treatment with the dibutyryl cyclic nucleotide, as was shown during tumor regression due to hormonal deprivation. Growth arrest, thus, appears to derive from enhanced tissue catabolism.     

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.     

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.     

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.     

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 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.     

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.     

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.     

Role of serotonergic input in the regulation of the beta-adrenergic receptor-coupled adenylate cyclase system

The action of desipramine on the norepinephrine-sensitive adenylate cyclase system and the density of beta-adrenergic receptors in rat cortex was studied after selective lesioning of serotonergic neurons with 5,7-dihydroxytryptamine. In animals with lesions desipramine failed to reduce the density of beta-adrenoceptors but decreased the response of adenosine 3',5'-monophosphate to isoproterenol and norepinephrine to the same degree as in animals without lesions. The results demonstrate a functional linkage between serotonergic and noradrenergic systems in the rat cortex, with beta-adrenergic receptors and neurohormonal sensitivity of the adenosine 3',5'-monophosphate-generating system being under separate regulatory control.     

Cyclic adenosine monophosphate: andromimetic action on seminal vesicular enzymes

Administration of adenosine 3',5'-monophosphate with theophylline produced testosterone-like induction of hexokinase, phosphofructokinase, pyruvate kinase, and glucose-6-phosphate dehydrogenase in the seminal vesicles of both orchidectomized and immature rats. The N(6)-O(2)'-dibutyryl analog of this cyclic nucleotide produced greater increases in vesicular enzyme activities than those induced by the parent compound. The observed enhancement of the key glycolytic enzymes and of hexose monophosphate shunt dehydrogenase was significantly inhibited by actinomycin D and cycloheximide. The evidence indicates that cyclic adenosine monophosphate may be involved as an intermediary in the action of androgenic hormones on male accessory sex organs.     

Growth inhibition by adenosine 3',5-monophosphate derivatives does not require 3',5' phosphodiester linkage

Analogs of adenosine 3',5'-monophosphate (cyclic AMP) inhibit the growth of cultured cell lines. The effects of 8-bromo- and N6-butyryl-substituted analogs of cyclic and noncyclic AMP on six cell lines were examined and were equally inhibitory. Variant cell lines with altered cyclic AMP-dependent protein kinase were more resistant to both cyclic and noncyclic nucleotides. We conclude that growth inhibition by analogs of cyclic AMP (i) does not require a 3',5' phosphodiester bond and (ii) may be mediated by a pathway involving endogenous cyclic AMP.     

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.     

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: 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.     

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.