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At least 19 recordsLinked to original sources
PubMed1978

Cyclic nucleotides, cyclic nucleotide phosphodiesterase, and development in Myxococcus xanthus.

Exogenous cyclic nucleotide phosphodiesterase (PD) accelerated fruiting body (FB) formation and increased territory size of aggregates in Myxococcus xanthus. Both guanosine 3'5'-monophosphate (cGMP) and guanosine 5'-monophosphate (GMP) were antagonistic to the PD effect. Adenosine 3'5'-monophosphate (cAMP) increases FB numbers twofold in the absence but not in the presence of PD. PD induction is not affected by methionine or isoleucine, which inhibit, or by threonine, which stimulates, FB formation. There is an increase and subsequent decrease in cAMP levels during early glycerol-induced microcyst development but 10 mM theophylline or caffeine not only inhibited microcyst development but induced germination in the presence of glycerol. On the basis of these results and the reports of other investigators a tentative model is proposed based on a dual role for cyclic nucleotides in the development in M. xanthus.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1979

The influence of 8-Br 3', 5'-cyclic nucleotide analogs and of inhibitors of 3', 5'-cyclic nucleotide phosphodiesterase, on noradrenaline secretion and neuromuscular transmission in guinea-pig vas deferens.

The effects of 3', 5'-cyclic nucleotide phosphodiesterase (PDE) inhibitors and of 8-Br 3', 5'-cyclic nucleotide analogs on nerve-muscle transmission were studied in the guinea-pig vas deferens preincubated with 3H-noradrenaline. 8-Br cyclic AMP and the PDE inhibitors 3-isobutyl-1-methylxanthine (IBMX) and 3-propionyl-4-hydrazinopyrazolopyridine (SQ 20006) enhanced the secretion of 3H-NA evoked by transmural nerve stimulation. 8-Br cyclic GMP was without effect in this respect. The muscle contraction evoked by transmural nerve stimulation, high potassium or by application of exogenous noradrenaline was depressed by IBMX and SQ 2006. The contraction evoked by transmural nerve stimulation was enhanced by 8-Br cyclic AMP and depressed by 8-Br cyclic GMP. These findings suggest differential involvement of 3', 5'-adenosine- and guanosine-cyclic nucleotides in excitation-secretion-coupling in the noradrenergic sympathetic nerves, and in excitation-contraction-coupling in the smooth muscle, of guinea-pig vas deferens.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Effects of coronary vasodilator on cyclic nucleotides. The concentrations of cyclic AMP and cyclic GMP in canine coronary artery and left ventricular muscle following the administration of various coronary vasodilators.

We examined the effects of various coronary vasodilator drugs, papaverine, dipyridamole, isosorbide dinitrate, amyl nitrite, nitroglycerin, diltiazem, and nifedipine, on cyclic nucleotides of the coronary artery and left ventricular muscle of anesthetized dogs at maximum coronary blood flow after the administration of each agents. Only papaverine and dipyridamole significantly increased the concentration of c-AMP in the coronary artery. Nitroglycerin and siosorbide dinitrate did not significantly change the concentration of c-AMP but rather increased the concentration of c-GMP. Coronary vasodilator drugs were divided into three groups in association with the relationship of cyclic nucleotides in the coronary artery. Group I, including papaverine, dipyridamole, and amyl nitrite, increased the concentration of c-AMP and the ratio of c-AMP to c-GMP. Group II, including nitroglycerin and isosorbide dinitrate, incrased the concentration of c-GMP and decreased the ratio of c-AMP to c-GMP. Group III, including nifedipine and diltiazem, had no effect on the cyclic nucleotides. Group I drugs also increased the concentration of c-AMP in the left ventricular muscle and so group I drugs may predispose the ischemic heart to develop ventricular arrhythmias. It seems that the most useful coronary vasodilator is no effect on the c-AMP in the ventricular muscle and group II and group III drugs are more useful coronary vasodilator drugs than group I drugs.

Amyl Nitrite↗
PubMed1979

[The influence of ether anesthesia in white mice on the contents of cyclic nucleotides in their brain and of cyclic nucleotides and glycogen in their liver (author's transl)].

During ether narcosis (10% diethyl ether v/v) of 30 min in white mice, the brain content of cAMP and cGMP is significantly diminished. By contrast, the liver cAMP and cGMP concentrations are increased 5 and 30 min after beginning narcosis but there is no or little difference, respectively, as compared to controls after 60 min. Liver glycogen content is elevated after 5 min but is diminished after 30 and 60 min as compared to controls. Pretreatment of the animals with the alpha-blocking agent phentolamine and the beta-blocking agent propranolol, respectively, prevents neither the increase in liver cAMP nor the decrease in liver glycogen during ether narcosis. It may be assumed that the changes in the liver and brain contents of cAMP and cGMP during ether application are due to physico-chemical alterations at the cell membrane which result in changes of the activity of the enzymes adenylate cyclase and guanylate cyclase in brain and liver tissue.

Anesthesia↗
PubMed1976

Binding of adenosine 3',5'-monophosphate dependent protein kinase regulatory subunit to immobilized cyclic nucleotide derivatives.

Several cyclic nucleotide derivatives with aminoalkyl side chains attached to the purine ring were synthesized and their interactions with adenosine 3',5'-monophosphate (cAMP) dependent protein kinase were studied before and after immobilization to CNBr-activated Sepharose 4B. The soluble N6-substituted derivatives were as effective as cAMP itself in activating protein kinase and were more effective than 8-substituted cAMP derivatives, whereas the 2-substituted cAMP derivatives and the cGMP derivatives were the least effective. All of the synthetic derivatives tested were poor substrates for beef heart phosphodiesterase being hydrolyzed at rates less than 2% for that of cAMP itself. Utilizing methodology developed to evaluate the affinity of protein kinase for immogilized cyclic nucleotides it was found that all of the immobilized cyclic nucleotides interacted with protein kinase in a biospecific manner as judged by the following criteria: (1) the immobilized cyclic nucleotides competed with cAMP for the binding sites on protein kinase; (2) the analogous spacer-arm did not compete; and (3) the effects of enzyme concentration, MgATP, and cleavage of the cyclic phosphate ring on the interactions of protein kinase with the immobilized cyclic nucleotides were the same as previously shown for free cAMP. In addition, the immobilized ligands were bound with the same order of effectiveness as the analogous soluble ligand. The observed Ka for the activation of 0.005 muM protein kinase by N6-H2N(CH2)2-cAMP was increased from 0.23 to 3 muM by the process of immobilization. This increase was unaffected by the coupling density and spacer-arm length. The observed Kb for 0.10 muM protein kinase binding to immobilized N6-H2N(CH2)2-cAMP was increased as the molecular sieving exclusion limit of the matrix used was decreased indicating that at least part of this decrease in apparent affinity upon immobilization is due to exclusion of the enzyme from a portion of the matrix and therefore of the immobilized ligand molecules.

Adenosine Triphosphate↗
PubMed1978

Synaptic potentials in sympathetic ganglia: are they mediated by cyclic nucleotides?

The hypothesis that cyclic nucleotides are intracellular second messengers mediating the generation of synaptic potentials was studied in the sympathetic ganglia of the bullfrog. Synaptic potentials and the effect of administering cyclic nucleotides and agents which affect cyclic nucleotide metabolism were recorded by the sucrose gap technique. The administration of adenosine 3',5'-monophosphate (cyclic AMP), guanosine 3',5'-monophosphate (cyclic GMP), or several of their derivatives produced little or no change in membrane potential. Prostaglandin E1 did not block the generation of postsynaptic potentials. Theophylline produced membrane effects that were different from those associated with postsynaptic potential generation; it also reduced the slow excitatory postsynaptic potential (EPSP) and potentiated the slow inhibitory postsynaptic potential (IPSP). The administration of papaverine, however, reduced both the slow EPSP and the slow IPSP. Although synaptic stimulation increases both cyclic GMP and cyclic AMP in these neurons, these results raise the possibility that these cyclic nucleotides may have functionla roles other than mediation of synaptic potentials.

Action Potentials↗
PubMed1978

Characterization of soluble uterine cyclic nucleotide phosphodiesterase.

Soluble cyclic nucleotide phosphodiesterase of rat uterus displays distinct structural and regulatory properties. Like phosphodiesterases from many mammalian sources the soluble uterine enzyme system exhibits nonlinear Lineweaver--Burk kinetics with cyclic adenosine 3':5'-monophosphate (cAMP) as substrate (apparent Kms congruent to 3 and 20 micron) and linear kinetics with cyclic guanosine 3':5'-monophosphate (cGMP) as substrate (apparent Km congruent to 3 micron). Unlike most other mammalian phosphodiesterases, however, numerous separation procedures reveal only a single form of uterine phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP. A single form of the enzyme is observed upon sucrose gradient centrifugation (7.9 S), agarose gel filtration, and DEAE-cellulose chromatography at either pH 8.0 OR 6.0. Heat denaturation (50 degrees C) of soluble uterine phosphodiesterase causes the loss of both cAMP and cGMP hydrolytic activities at the same rate. Isoelectric focusing reveals major (pI = 5.2) and minor forms (pI = 5.8) of phosphodiesterase which both catalyze the hydrolysis of the two cyclic nucleotide substrates. In vivo administration of estradiol produces identical decreases in the activities of cAMP and cGMP phosphodiesterase. These results raise the possibility that the uterus contains a single form of soluble phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Cyclic nucleotides and platelet aggregation. Effect of aggregating agents on the activity of cyclic nucleotide-metabolizing enzymes.

The activities of adenylate and guanylate cyclase and cyclic nucleotide 3':5'-phosphodiesterase were determined during the aggregation of human blood platelets with thrombin, ADP, arachidonic acid and epinephrine. The activity of guanylate cyclase is altered to a much larger degree than adenylate cyclase, while cyclic nucleotide phosphodiesterease activity remains unchanged. During the early phases of thrombin-and ADP-induced platelet aggregation a marked activation of the guanylate cyclase occurs whereas aggregation induced by arachidonic acid or epinephrine results in a rapid diminution of this activity. In all four cases, the adenylate cyclase activity is only slightly decreased when examined under identical conditions. Platelet aggregation induced by a wide variety of aggregating agents including collagen and platelet isoantibodies results in the "release" of only small amounts (1-3%) of guanylate cyclase and cyclic nucleotide phosphodiesterase and no adenylate cyclase. The guanylate cyclase and cyclic nucleotide phosphodiesterase activities are associated almost entirely with the soluble cytoplasmic fraction of the platelet, while the adenylate cyclase if found exclusively in a membrane bound form. ADP and epinephrine moderately inhibit guanylate and adenylate cyclase in subcellular preparations, while arachidonic and other unsaturated fatty acids moderately stimulate (2-4-fold) the former. It is concluded that (1) the activity of platelet guanylate cyclase during aggregation depends on the nature and mode of action of the inducing agent, (2) the activity of the membrnae adenylate cyclase during aggregation is independent of the aggregating agent and is associated with a reduction of activity and (3) cyclic nucleotide phosphodiesterase remains unchanged during the process of platelet aggregation and release. Furthermore, these observations suggest a role for unsaturated fatty acids in the control of intracellular cyclic GMP levels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Plasma cyclic nucleotide levels in hyperthyroidism.

Plasma cyclic AMP and cyclic GMP levels were studied in a group of normal subjects and 10 subjects with hyperthyroidism. In the control group, mean plasma cyclic AMP levels were 15.3 +/- 1.3 nmol/l (SEM), and plasma cyclic GMP levels were 9.4 +/- 0.58 nmol/l (SEM). In untreated hyperthyroid subjects, both plasma cyclic AMP and cyclic GMP levels were significantly elevated above normal with mean values of 35.0 +/- 2.4 nmol/l (SEM) (P less than 0.001) and 14.7 +/- 0.2 nmol/l (SEM), (P less than 0.001), respectively. Six of the hyperthyroid subjects were re-studied when they became euthyroid; plasma cyclic nucleotide concentrations all fell within the normal range. To evaluate the relative contribution of triiodothyronine and thyroxine to elevated plasma cyclic nucleotide levels, two hyperthyroid subjects were treated with propylthiouracil and iodide. Plasma cyclic nucleotide levels were normalized when plasma triiodothyronine levels declined to normal range, at the time when plasma thyroxine levels were still elevated. These preliminary data suggest that increased triiodothyronine production is responsible for the increased cyclic nucleotide levels in hyperthyroidism.

Adult↗