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.     

Biosynthesis of biopterin: adrenergic cyclic adenosine monophosphate-dependent inhibition in the pineal gland

Pineal glands in organ culture synthesize and release biopterin and are able to maintain concentrations of biopterin occurring in vivo for up to 54 hours in vitro. The intracellular biopterin content is reduced 50 percent by treatment with l-norepinephrine or cyclic adenosine monophosphate derivatives, but not by d-norepinephrine. This is an indication that biopterin levels are regulated by an adrenergic cyclic adenosine monophosphate-dependent mechanism. The decline in tissue biopterin content, produced mainly by inhibited of biosynthesis, is maximal at 6 hours and is not associated with either an increase in biopterin release or a shift in the reduction state of the biopterin.     

Cyclic adenosine monophosphate: possible mediator for norepinephrine effects on cerebellar Purkinje cells

Microelectrophoretic application of norepinephrine or cyclic adenosine monophosphate reduces the discharge frequency of Purkinje cells in the rat cerebellum. In contrast, other nucleotides accelerate the discharge rate of most units. Parenterally administered theophylline, which inhibits the hydrolysis of cyclic adenosine monophosphate enhances the effects of norepinephrine and cyclic adenosine monophosphate. Therefore, norepinephrine may be able to regulate Purkinje cells functionally by metabolic stimulation of cyclic adenosine monophosphate synthesis.     

Cyclic adenosine and guaosine monophosphates and gucagon: effect on liver membrane potentials

Cyclic adenosine monophosphate, cyclic guanosine monophosphate, glucagon, and isoproterenol each hyperpolarized perfused rat liver cells. The hyperpolarization followed a time course similar to the stimulated increase in potassium efflux and was preceded by the increase in calcium efflux. The hyperpolarization induced by cyclic adenosine monophosphate was blocked by tetracaine. The similarity of the action of the cyclic nucleotides to that of glucagon supports the hypothesis that cyclic adenosine monophosphate is the secondary messenger mediating the action of glucagon.     

Cyclic adenosine monophosphate: stimulation of melatonin and serotonin synthesis in cultured rat pineals

Dibutyryl cyclic adenosine monophosphate, like norepinephrine, stimulates the synthesis of labeled melatonin and serotonin from tryptophan labeled with carbon-14 by rat pineals in organ culture. Unlike norepinephrine, dibutyryl cyclic adenosine monophosphate does not enhance the accumulation of labeled tryptophan or protein within the pineal. These findings are compatible with the hypothesis that cyclic adenosine monophosphate mediates some, but not all, of the effects of norepinephrine.     

Noradrenergic stimulation of cyclic adenosine monophosphate in rat Purkinje neurons: an immunocytochemical study

A specific immunofluorescent histochemical method for cyclic adenosine monophosphate was used to study rat cerebellum. After topical treatment with norepinephrine or stimulation of norepinephrine-containing afferents from locus coeruleus, there was a striking increase in the number of Purkinje cells with strong cyclic adenosine monophosphate reactivity. Other putative inhibitory transmitters had no significant effect on staining of Purkinje cells. The results provide the first histochemical support for the hypothesis that cyclic adenosine monophosphate can be generated postsynaptically in central neurons in response to noradrenergic stimuli.     

Cyclic adenosine monophosphate phosphodiesterase in brain: effect on anxiety

Drugs that reduce anxiety may be mediated by cyclic adenosine monophosphate in the brain because (i) potent anxiety-reducing drugs are also potent inhibitors of brain phosphodiesterase activity; (ii) dibutyryl cyclic adenosine monophosphate has the ability to reduce anxiety; (iii) the methylxanthines show significant anxiety-reducing effects; (iv) theophylline and chlordiazepoxide produce additive anxiety-reducing activity; and (v) there is a significant correlation between the anxiety-reducing property of drugs and their ability to inhibit phosphodiesterase activity in the brain.     

Cyclic adenosine monophosphate in brain areas: microwave irradiation as a means of tissue fixation

Amounts of cyclic adenosine monophosphate in discrete regions of the brain were estimated after exposure of rats to microwave irradiation. Amounts were highest in the cerebellum and brainstem, intermediate in the hypothalamus and midbrain, and lowest in the hippocampus and cortex. Decapitation increased the concentration of cyclic adenosine monophosphate in all brain areas, although the increase in the cerebellum was three to four times greater than that in other areas. Microwave irradiation may provide a means of rapidly fixing brain tissue in situ while permitting easy dissection of the brain. In this way artifacts produced by decapitation can be eliminated, and concentrations of heat-stable compounds in the brain can be estimated under conditions which more closely approximate those in vivo.     

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.     

Cyclic adenosine monophosphate: potassium-dependent action on vascular smooth muscle membrane potential

Dibutyryl cyclic adenosine monophosphate and theophylline hyperpolarize smooth muscle of rabbit main pulmonary artery in low concentrations of potassium (1 millimole per liter) but do not have a significant effect on the membrane potential in the presence of high concentrations of potassium (10 millimoles per liter). The dependence of the hyperpolarizing effect on a low external concentration of potassium is similar to that observed with isoproterenol. Prior treatment with theophylline potentiated the hyperpolarizing action of isoproterenol. These findings are compatible with the assumption that potassium-dependent, beta-adrenergic hyperpolarization is mediated by cyclic adenosine monophosphate.     

Renal adenyl cyclase: anatomically separate sites for parathyroid hormone and vasopressin

Adenyl cyclase from plasma membrane fractions of rat renal cortex or medulla was assayed by measuring conversion of adenosine triphosphate labeled at the alpha-phosphate with (32)P to cyclic 3',5'-adenosine monophosphate labeled with 32P. Parathyroid hormone activated the enzyme primarily in cortex; vasopressin acted primarily in medulla. These experiments support the conclusion that cyclic adenosine monophosphate mediates the action of parathyroid hormone on the kidney and show that parathyroid hormone and vasopressin stimulate adenyl cyclase at anatomically separable areas within the kidney.     

Phosphodiesterase in Dictyostelium discoideum and the chemotactic response to cyclic adenosine monophosphate

A phosphodiesterase with a low Michaelis constant for cyclic adenosine monophosphate was found in the membrane fraction of the cellular slime mold. This activity was highest during the aggregation stage. Enzyme with similar properties was also secreted by the cells. Dithiothreitol inhibited both enzymes and potentiated the cellular response to cyclic adenosine monophosphate.     

Cyclic adenosine monophosphate and norepinephrine: effects on transmembrane properties of cerebellar Purkinje cells

Electrical properties of Purkinje cells were recorded by intracellular microelectrode during extracellular electrophoretic application of gamma aminobutyrate, norepinephrine, cyclic adenosine monophosphate, and dibutyryl cyclic adenosine monophosphate. All these substances hyperpolarized Purkinje cells. Transmembrane resistance decreased during gamma aminobutyrate hyperpolarization. In contrast, norepinephrine and the cyclic nucleotides generally elevated resistance. These results show that cyclic nucleotides mimic the unique effects of norepinephrine on the bioelectric properties of neuronal membranes.     

Isolated adrenal cells: adrenocorticotropic hormone, calcium, steroidogenesis, and cyclic adenosine monophosphate

Corticosterone production by isolated adrenal cells in response to adrenocorticotropic hormone is reduced when the cells are incubated in a medium that contains no calcium. This reduction is associated with an equal reduction of accumulation of cyclic adenosine monophosphate. Production of corticosterone and accumulation of cyclic adenosine monophosphate are increased when the calcium concentration in the medium is increased (from zero to 7.65 millimolar). This is in contrast to the situation in "subcellular membrane fragments" of adrenal tissue where high calcium in the medium (> 1.0 millimolar) inhibits cyclic adenosine monophosphate accumulation. We propose that adenyl cyclase in the intact plasma membrane is located in a compartment wherein calcium concentration is low and remains unaffected by the concentration of calcium in the extracellular space. It is proposed that, as the concentration of calcium in the incubation medium is increased from zero to 7.65 millimolar, the strength of the signal generated by the interaction of adrenocorticotropic hormone with its receptor and transmitted to the adenyl cyclase compartment is proportionately increased.     

Regulation of phosphodiesterase synthesis: requirement for cyclic adenosine monophosphate-dependent protein kinase

Endogenous cyclic adenosine monophosphate (AMP) and its dibutyryl derivative increase cyclic AMP phosphodiesterase activity in cultured lymphoma cells. This effect is prevented by cycloheximide. A variant population of cells deficient in cyclic AMP-dependent protein kinase contains lower basal phosphodiesterase activity, which cannot be induced by cyclic AMP.     

Tripeptide structure of bursin, a selective B-cell-differentiating hormone of the bursa of fabricius

Differentiation of lymphoid precursor cells in a variety of species is induced by polypeptide hormones such as thymopoietin for T cells and bursin for B cells. In the present experiments, bursin isolated from the bursa of Fabricius of chicken was found to induce the phenotypic differentiation of mammalian and avian B precursor cells but not of T precursor cells in vitro. Similarly, bursin increased cyclic guanosine monophosphate in cells of the human B-cell line Daudi but not in cells of the human T-cell line CEM. These inducing properties of bursin are the reverse of the inducing properties of thymopoietin produced by the thymus and are appropriate to a physiological B-cell-inducing hormone. A tripeptide sequence (lysyl-histidyl-glycyl-amide) was determined for bursin and confirmed by synthesizing this proposed structure and demonstrating chemical identity of the natural and synthetic peptides. Similarity of biological action was indicated in induction assays by elevation of cyclic adenosine monophosphate and guanosine monophosphate in Daudi B cells but not in CEM T cells.     

Thyrotropin and cyclic nucleotide effects on prostaglandin levels in isolated thyroid cells

Thyrotropin increases prostaglandin levels in isolated thyroid cells. Since comparable results were obtained with butyrated cyclic adenosine monophosphate derivatives as well as with the phosphodiesterase inhibitors quazodine and theophylline, it appears that cyclic adenosine monophosphate mediates this effect of thyrotropin. These observations suggest that intracellular prostaglandins play a role in modulating thyrotropin action on thyroid.     

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.     

AP液对家兔血浆环核苷酸（cAMP、cGMP）含量影响的研究

 用放射免疫分析法（RIA）测定健康家兔血浆cAMP、cGMP含量，观察AP液对环核苷酸的影响。实验结果表明，AP液能促使cAMP、cGMP水平都明显增高，两者与试验前相比，差异均极显著（P＜0.01）、且比值基本不变。鉴于环核苷酸可作为植物性神经功能的指标，因而本项研究为植物性神经高阈平衡论提供了分子生物学水平的论据。     

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.