Cyclic nucleotides and their relationship to complement-component-C2 synthesis by human monocytes

The time courses of changes in cyclic nucleotide levels in monocytes have been studied. Histamine and prostaglandin E2 (PGE2) produced a rapid rise in cyclic AMP (peak 15 min) levels, which returned to normal within 4h, whereas cholera toxin, NaF and phosphodiesterase inhibitors produced slow sustained rises lasting over 24h. With the exception of isobutylmethylxanthine (10 mumol X 1(-1), none of these reagents altered cyclic GMP levels. alpha 1-Adrenergic and nicotinic cholinergic receptor-ligand interactions and imidazole produced rapid and relatively short-lived falls in cyclic AMP, and rises in cyclic GMP. In contrast, prostaglandin synthetase inhibitors produced delayed but more sustained falls in cyclic AMP but no rises in cyclic GMP. Agents that increased cyclic AMP decreased complement-component-C2 production, and those that decreased cyclic AMP increased C2 production. Agents that increased cyclic GMP alone (ascorbate, nitroprusside and prostaglandin F2 alpha) did not affect C2 production. Antigen-antibody complexes that stimulate C2 synthesis produced falls in cyclic AMP and rises in cyclic GMP similar to those produced by adrenergic and cholinergic ligands. Serum-treated complexes and anaphylatoxins, which inhibited C2 production, were associated with changes in cyclic AMP similar to those produced by histamine and PGE2. These data suggest that there are two transmembrane signals involved in the regulation of C2 production by monocytes. The inhibitory signal is adenylyl cyclase activation. The stimulatory signal is not so obvious, but may be Ca2+ influx, since the time courses of changes in cyclic nucleotides produced by agents that stimulate C2 synthesis are identical, and alpha 1-adrenergic agonists cause the formation of Ca2+ channels.

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The Role of Cyclic Nucleotides in the CNS

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s031716710002521x ◽

1977 ◽

Vol 4 (3) ◽

pp. 151-195 ◽

Cited By ~ 88

Author(s):

John W. Phillis

Keyword(s):

Cyclic Amp ◽

Synaptic Transmission ◽

Cyclic Gmp ◽

Adenosine Receptor ◽

Cyclic Nucleotides ◽

Phosphodiesterase Inhibitors ◽

Adenosine Uptake ◽

Injection Techniques ◽

Firm Basis

SUMMARY:On the basis of the information presented in this review, it is difficult to reach any firm decision regarding the role of cyclic AMP (or cyclic GMP) in synaptic transmission in the brain. While it is clear that cyclic nucleotide levels can be altered by the exposure of neural tissues to various neurotransmitters, it would be premature to claim that these nucleotides are, or are not, essential to the transmission process in the pre- or postsynaptic components of the synapse. In future experiments with cyclic AMP it will be necessary to consider more critically whether the extracellularly applied nucleotide merely provides a source of adenosine and is thus activating an extracellularly located adenosine receptor, or whether it is actually reaching the hypothetical sites at which it might act as a second messenger. The application of cyclic AMP by intracellular injection techniques should minimize this particular problem, although possibly at the expense of new difficulties. Prior blockade of the adenosine receptor with agents such as theophylline or adenine xylofuranoside may also assist in the categorization of responses to extracellularly applied cyclic AMP as being a result either of activation of the adenosine receptor or of some other mechanism. Ultimately, the development of highly specific inhibitors for adenylate cyclase should provide a firm basis from which to draw conclusions about the role of cyclic AMP in synaptic transmission. Similar considerations apply to the actions of cyclic GMP and the role of its synthesizing enzyme, guanylale cyclase.The use of phosphodiesterase inhibitors in studies on cyclic nucleotides must also be approached with caution. The diverse actions of many of these compounds, which include calcium mobilization and block of adenosine uptake, could account for many of the results that have been reported in the literature.

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A homogeneous immunoassay for cyclic nucleotides based on chemiluminescence energy transfer

Biochemical Journal ◽

10.1042/bj2160185 ◽

1983 ◽

Vol 216 (1) ◽

pp. 185-194 ◽

Cited By ~ 30

Author(s):

A K Campbell ◽

A Patel

Keyword(s):

Energy Transfer ◽

Cyclic Amp ◽

Cyclic Gmp ◽

Immunoglobulin G ◽

Cyclic Nucleotides ◽

Solid Phase ◽

Complement Component ◽

Radiative Energy ◽

Homogeneous Immunoassay ◽

Radiative Energy Transfer

A chemiluminescent derivative of cyclic AMP, aminobutylethylisoluminol succinyl cyclic AMP (ABEI-scAMP), was synthesized in order to develop a homogeneous immunoassay based on non-radiative energy transfer. ABEI-scAMP was chemiluminescent (5.1 × 10(18) luminescent counts X mol-1 at pH 13), pure (greater than 95%) stable and immunologically active. A conventional immunoassay was established using ABEI-scAMP and a solid-phase anti-(cyclic AMP) immunoglobulin G which could detect cyclic AMP at least down to 25fmol. A homogeneous immunoassay for cyclic AMP was established by measuring the shift in wavelength from 460 to 525nm which occurred when ABEI-scAMP was bound to fluorescein-labelled anti-(cyclic AMP) immunoglobulin G. The assay was at least as sensitive as the conventional radioimmunoassay using cyclic [3H]AMP and could measure cyclic AMP over the range 1-1000nM. The homogeneous chemiluminescent energy transfer assay was also able to quantify the association and dissociation of antibody-antigen complexes. Chemiluminescence energy transfer occurred between fluorescein-labelled antibodies and several other ABEI-labelled antigens (Mr values 314-150000) including progesterone, cyclic GMP, complement component C9 and immunoglobulin G. The results provide a homogeneous immunoassay capable of measuring free cyclic AMP under conditions likely to exist inside cells.

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Effect of Cyclic AMP and Cyclic GMP on Thromboplastin (Factor III) Synthesis in Human Monocytes In Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665317 ◽

1983 ◽

Vol 50 (04) ◽

pp. 804-809 ◽

Cited By ~ 16

Author(s):

Torstein Lyberg

Keyword(s):

Cyclic Amp ◽

Cyclic Gmp ◽

Immune Complexes ◽

Phosphodiesterase Inhibitors ◽

Inhibitory Effect ◽

Intracellular Camp ◽

Human Monocytes ◽

Purified Protein Derivative ◽

A 23187

SummaryHuman monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-0-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac -4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 201724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA arid IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.

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Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin–pancreozymin

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y79-082 ◽

1979 ◽

Vol 57 (6) ◽

pp. 541-546 ◽

Cited By ~ 3

Author(s):

H. L. Cailla ◽

H. Sarles ◽

M. V. Singer

Keyword(s):

Cyclic Amp ◽

Pancreatic Juice ◽

Cyclic Gmp ◽

Cyclic Nucleotides ◽

Parallel Increase ◽

Calcium Bicarbonate ◽

Strong Linear Correlation ◽

Protein Output ◽

Dose Dependent ◽

Stimulation Of

The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin–pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg−1 h−1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg−1 h−1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg−1 h−1 of CCK and later for 12 and 24 U kg−1 h−1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.

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Differential effects of cyclic nucleotides and their analogs and various agents on cyclic GMP-specific and cyclic AMP-specific phosphodiesterases purified from guinea pig lung

Biochemical Pharmacology ◽

10.1016/0006-2952(78)90261-7 ◽

1978 ◽

Vol 27 (1) ◽

pp. 89-95 ◽

Cited By ~ 22

Author(s):

Craig W. Davis ◽

J.F. Kuo

Keyword(s):

Cyclic Amp ◽

Guinea Pig ◽

Cyclic Gmp ◽

Cyclic Nucleotides ◽

Differential Effects

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THE MODULATING INFLUENCE OF CYCLIC NUCLEOTIDES UPON LYMPHOCYTE-MEDIATED CYTOTOXICITY

Journal of Experimental Medicine ◽

10.1084/jem.138.2.381 ◽

1973 ◽

Vol 138 (2) ◽

pp. 381-393 ◽

Cited By ~ 126

Author(s):

Terry B. Strom ◽

Charles B. Carpenter ◽

Marvin R. Garovoy ◽

K. Frank Austen ◽

John P. Merrill ◽

...

Keyword(s):

Cyclic Amp ◽

Adenylate Cyclase ◽

Cyclic Gmp ◽

Cyclic Nucleotides ◽

Prostaglandin E1 ◽

Cell Interaction ◽

Target Cells ◽

Cholinergic Stimulation ◽

Initial Cell ◽

Initial Interaction

The capacity of allosensitized thymus-derived lymphocytes to destroy target cells bearing donor alloantigens is modulated by the cellular levels of cyclic AMP and cyclic GMP. Increases in the cyclic AMP levels of attacking lymphocytes by stimulation with prostaglandin E1, isoproterenol, and cholera toxin inhibit lymphocyte-mediated cytotoxicity; whereas, depletion of cyclic AMP with imidazole enhances cytotoxicity. The augmentation of cytotoxicity produced by cholinergic stimulation with carbamylcholine is not associated with alterations in cyclic AMP levels and is duplicated by 8-bromo-cyclic GMP. The effects of activators of adenylate cyclase, cholinomimetic agents, and 8-bromocyclic GMP are upon the attacking and not the target cells and occur at the time of initial interaction of attacking and target cells. Indeed, the level of cyclic nucleotide (cyclic AMP and cyclic GMP) at the time of initial cell-to-cell interaction determines the extent of cytotoxicity.

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Growth hormone, cyclic nucleotides and the rapid control of translation in heart muscle

Biochemical Journal ◽

10.1042/bj1520583 ◽

1975 ◽

Vol 152 (3) ◽

pp. 583-592 ◽

Cited By ~ 13

Author(s):

J Mowbray ◽

J A Davies ◽

D J Bates ◽

C J Jones

Keyword(s):

Growth Hormone ◽

Protein Synthesis ◽

Cyclic Amp ◽

Cyclic Gmp ◽

Cyclic Nucleotides ◽

Cyclic Nucleotide ◽

Precursor Pool ◽

Growth Hormone Action ◽

Constant Rate ◽

The Individual

Perfused rat heart incorporated L-[14C]tyrosine into protein at a constant rate for up to 75 min. A purified bovine growth-hormone preparation (1 mug/ml) stimulated the incorporation to a new constant rate that was more than three times the control rate by 10 min after hormone addition to perfusate. The hormone, however, did not alter the intracellular tracer amino acid pool, and the relationship of this to the aminoacyl-tRNA precursor pool is discussed. It is concluded that the increased incorporation largely reflected a rapid increase in protein synthesis at the ribosomes. Measurements of cyclic nucleotide contents during the perfusion showed that these appeared to vary in a systematic way during the perfusion. This strands in contrast with the constant values given by several other parameters measured in this preparation. Futher, the cyclic nucleotide variation seems to be independent of external effectors. The steady-state performance of the heart correlates more closely the [cyclic AMP]/[cyclic GMP] ratio than with the content of the individual cyclic nucleotides. At 10 min after the addition of growth hormone a slight decrese in cyclic AMP content and a large decrease in cyclic GMP were found, suggesting that the hormone's effect in stimulating protein synthesis may be mediated by a decrease in cyclic nucleotide concentrations or an increase in the [cyclic AMP]/[cyclic |p] ratio. The findings are also consistent with an intracellularly directed role for these nucleotides, and the possibility that the cyclic nucleotide changes are an indirect result of growth-hormone action is discussed.

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Immunofluorescent localization of cyclic nucleotide-dependent protein kinases on the mitotic apparatus of cultured cells.

The Journal of Cell Biology ◽

10.1083/jcb.87.2.336 ◽

1980 ◽

Vol 87 (2) ◽

pp. 336-345 ◽

Cited By ~ 42

Author(s):

C L Browne ◽

A H Lockwood ◽

J L Su ◽

J A Beavo ◽

A L Steiner

Keyword(s):

Protein Kinase ◽

Cyclic Amp ◽

Protein Kinases ◽

Cyclic Gmp ◽

Cyclic Nucleotides ◽

Mitotic Spindle ◽

Cyclic Nucleotide ◽

Dependent Protein Kinase ◽

Mitotic Apparatus ◽

Dependent Protein

Cyclic nucleotides and cyclic nucleotide-dependent protein kinases have been implicated in the regulation of cell motility and division, processes that depend on the cell cytoskeleton. To determine whether cyclic nucleotides or their kinases are physically associated with the cytoskeleton during cell division, fluorescently labeled antibodies directed against cyclic AMP, cyclic GMP, and the cyclic nucleotide-dpendent protein kinases were used to localize these molecules in mitotic PtK1 cells. Both the cyclic GMP-dependent protein kinase and the type II regulatory subunit of the cyclic AMP-dependent protein kinase were localized on the mitotic spindle. Throughout mitosis, their distribution closely resembled that of tubulin. Antibodies to cyclic AMP, cyclic GMP, and the type I regulatory and catalytic subunits of the cyclic AMP-dependent protein kinase did not label the mitotic apparatus. The association between specific components of the cyclic neucleotide system and the mitotic spindle suggests that cyclic nucleotide-dependent phosphorylation of spindle proteins, such as those of microtubules, may play a fundamental role in the regulation of spindle assembly and chromosome motion.

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