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.     

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.     

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 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.     

Calcium requirement for melanophore-stimulating hormone action on melanophores

The calcium ion is specifically required for the action of melanophorestimulating hormone on melanosome dispersion within lizard (Anolis carolinensis) melanophores in vitro. The response to this hormone is directly related to the concentration of the Ca(2+) ion. Lithium, choline, rubidium, and cesium will replace the sodium and potassium of Ringer solution if Ca(2+) is present. Calcium ions are not required for melanosome dispersion itself, since theophylline or dibutyryl cyclic adenosine monophosphate reversibly darkens lizard skins in the absence of calcium.     

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.     

Sodium and potassium effects on skeletal muscle microsomal adenosine triphosphatase and calcium uptake

The relationship between the (Na(+) and K(+))-activated adenosine triphosphatase enzyme system implicated in sodium-transport by cell membranes and the calcium-activated adenosine triphosphatase, which is generally associated with calcium uptake, was examined in microsomes from skeletal muscle. Whereas sodium and potassium did not modify the relatively low adenosine triphosphatase activity seen in the absence of calcium, a pattern similar to that of the sodium-transport enzyme system was seen afer the addition of CaCl(2). The calcium-activated adenosine triphosphatase was stimulated equally by sodium or potassium alone, but both the rate and extent of calcium uptake were enhanced more by potassium than by sodium at concentrations below 0.12 mole per liter. In the absence of either of these ions addition of calcium failed to activate adenosine triphosphatase although significant amounts of calcium were taken up by the microsomes.     

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.     

Protein kinase translocation as an early event in the hormonal control of uterine contraction

beta-Adrenergic stimulation with isoproterenol inhibits contractility, increases cyclic adenosine monophosphate (AMP) concentration, decreases the concentration of unsaturated cyclic AMP receptor sites, and increases cyclic AMP-independent kinase in the uterus of ovariectomized rats. The total soluble kinase activity is reduced. The protein kinase activity lost from the cytosol was translocated to the microsomal fraction mostly in a cyclic AMP-independent form, suggesting a particulate substrate for the activated enzyme.     

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.     

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.     

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.     

Thyroid-stimulating hormone and prostaglandin E1 stimulation of cyclic 3',5'-adenosine monophosphate in thyroid slices

Thyroid-stimulating hormone increased the cyclic 3',5'-adenosine monophosphate concentration in dog thyroid slices during a 1-minute incubation period and produced a maximum effect soon thereafter. The elevation persisted for at least 30 minutes. The concentrations of the cyclic 3',5'-adenosine monophosphate increased as the TSH concentration was increased from 0.125 to 50 milliunits per milliliter. Prostaglandin E(1), which increases glucose oxidation in dog thyroid slices, also increased the concentration of cyclic 3',5'-adenosine monophosphate. Although sodium fluoride stimulates thyroid adenyl cyclase, it did not increase concentration of cyclic 3',5'-adenosine monophosphate. Carbamylcholine and menadiol sodium diphosphate augment glucose oxidation in dog thyroid slices but do not change concentrations of cyclic 3',5'-adenosine monophosphate.     

Cyclic adenosine monophosphate and hypertension in rats

Aortas from spontaneously hypertensive and stress hypertensive rats contained significantly lower intracellular concentrations of cyclic adenosine monophosphate than did their respective controls. Adenylate cyclase activity was normal but was less responsive to stimulation, while phosphodiesterase activity (especially the low Michaelis-Menten constant form) was significantly elevated. Human aortas contained two forms of phosphodiesterase that were similar to those in rat aortas.     

牛蒡子苷对小鼠原代骨骼肌细胞磷酸二酯酶活性及细胞生长的影响

 【目的】以茶碱为参照,观察中药成分牛蒡子苷对原代骨骼肌细胞磷酸二酯酶（Phosphodiesterase,PDE）活性及蛋白质合成的影响,探讨中药通过抑制PDE促进肌肉生长的作用及机理。【方法】分离1～3日龄ICR小鼠四肢肌肉用于骨骼肌原代细胞培养,在培养至第5～6天时向培养基中添加不同浓度的牛蒡子苷和茶碱,以不含牛蒡子苷和茶碱的培养基为阴性对照,继续培养24 h,采用HPLC、ELISA以及考马斯亮蓝法分别测定骨骼肌细胞cAMP PDE的活性、细胞内cAMP水平以及细胞总蛋白质合成。【结果】牛蒡子苷终浓度达到2.5 μg•ml-1、茶碱终浓度为20 μg•ml-1时均能极显著抑制原代培养骨骼肌细胞cAMP PDE的活性(P＜0.01）,显著提高细胞内cAMP水平（P＜0.05）,极显著促进肌细胞总蛋白质的合成（P＜0.01）。【结论】中药成分牛蒡子苷具有通过调节骨骼肌细胞内PDE的活性和cAMP水平,增加肌细胞蛋白质合成,促进骨骼肌细胞生长的作用。结果提示对PDE有抑制作用的中药有望成为促进动物生长的新型饲料添加剂。     

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.     

Modulation of adenylate cyclase activity in liver and fat cell membranes by insulin

Insulin depresses both the activity of adenylate cyclase stimulated by glucagon, epinephrine, and sodium fluoride in liver cell membranes and the activity of adenylate cyclase stimulated by epinephrine and adrenocorticotropin in particulate preparations from homogenates of isolated fat cells. Significant inhibition is detected with very low concentrations (10(-11) molar) of insulin but not with unphysiologically high (10(-9)molar) concentrations of the hormone. These direct effects of insulin on an enzymatic system in broken-cell -preparations suggest a fundamental role of adenylate cyclase activity and of cyclic adenosine monophosphate in the mechanism of action of insulin.     

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.