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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activities of cyclic nucleotide phosphodiesterase were studied in rat uterus as a function of age, DNA and protein content. Linear kinetics were observed for uterine homogenate cyclic GMP (cGMP) phosphodiesterase activity, but anomalous double-reciprocal plots, suggestive of multiple enzyme forms, were observed for cyclic AMP (cAMP) hydrolysis, cAMP phosphodiesterase was therefore measured at high and low substrate concentrations, 200 muM and 0.25 muM cAMP, respectively, to approximate multiple enzyme activities. Based upon total organ content, the total cAMP and cGMP phosphodiesterase activities increased throughout uterine development, from 5-50 days of age. On the same basis, the apparent low KM cAMP phosphodiesterase increased only between days 5 and 15 and showed no significant increase between days 15 and 50. On the other hand, specific activities of an apparent low KM cAMP phosphodiesterase, expressed per mg of protein or per mug of DNA, showed a marked reduction in activity between 30 and 50 days of age. Chronic administration of 17beta-estradiol to immature rats increased their uterine protein content and decreased the specific activity of the apparent low KM cAMP phosphodiesterase. In another estrogen target tissue, the anterior pituitary, protein and DNA content also increased during development but no changes in specific activities of cyclic nucleotide phosphodiesterase were noted. These results suggest the possible participation of cyclic nucleotide phosphodiesterases in the induction of uterine growth and development by ovarian hormones.
Mol Cell Endocrinol 1975 Oct
PMID:Cyclic nucleotide phosphodiesterases in uterine development. 17 92

1. The action of insulin on plasma cyclic nucleotide concentrations in normal human subjects has been studied after intravenous injection, alone and in combination with glucagon. 2. After injection of insulin alone there was an initial small, though not significant, decrease in plasma cyclic AMP at 15 min followed by an increase to more than twice the initial concentration at 30 min. The increase was absent when hypoglycaemia was lessened by infusion of glucose after insulin injection. 3. Injection of insulin caused no significant change in plasma cyclic GMP concentration, whether or not glucose was infused after the hormone. 4. Glucagon (3-300 nmol, 10-1000 mug), caused a dose-dependent increase in plasma cyclic AMP concentration. The rise in plasma cyclic AMP produced by 3 or 30 nmol of glucagon was not significantly modified by simultaneous injection of insulin (44 nmol; 6 units).
Clin Sci Mol Med 1976 Jun
PMID:The effect of insulin on adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate concentrations in human plasma. 17 51

The in vitro effects of insulin on different phosphodiesterase activities present in rat epididymal fat cells from normal and hypothyroid rats have been studied. Evidence is presented that insulin increases the maximum velocity of a particulate, low Km, cyclic adenosine-3', 5'-monophosphate (cyclic AMP) phosphodiesterase in both types of cells, this effect being more clearly evident with the fat cells from hypothyroid animals; combination of insulin and thyroidectomy resulted in a 400% stimulation with 10-10 - 10-9 M insulin. A clear and significant effect was apparent at 10-11 M insulin. However, the dose-response curve was biphasic, since stimulation by insulin was suppressed for doses of hormone higher 10-8 - 10-7 M. Moreover, insulin effects were very fast, since clear stimulation was observed after only 2 min of incubation; the maximal increase was obtained after 10 min. Insulin did not significantly affect the soluble cyclic AMP phosphodiesterase activity in normal cells, thus confirming results obtained by others. However, the soluble cyclic AMP phosphodiesterase activity was clearly stimulated by insulin when the fat cells were prepared from hypothyroid rats. Maximal stimulation was obtained with 10-9 M insulin; the response was again very fast. Soluble cyclic GMP phosphodiesterase activity was also increased additively by hypothyroidism and insulin, maximal stimulation being obtained with 10-9 M insulin. With this dose of insulin the additive effects of thyroidectomy and insulin produced a 5-fold stimulation. The effect of insulin on the soluble cyclic GMP phosphodiesterase was very fast (2-5 min). With both soluble cyclic nucleotide phosphodiesterase activities, insulin increased the maximal velocity but not apparent Km of the enzyme. Thus, hypothyroidism and insulin produced additive effects suggesting a different mechanism of action of these two hormonal situations on the degradation of the intracellular pools of cyclic AMP and cyclic GMP.
Mol Cell Endocrinol
PMID:Cyclic nucleotide phosphodiesterases, insulin and thyroid hormones. 18 75

Carbachol increased amylase release and K+ efflux from rat parotid tissue slices. The amount of amylase released was small compared to that released by isoproterenol. The effect of carbachol on amylase release and K+ efflux was a direct effect. This conclusion was based on the finding that the stimulatory effects of carbachol were blocked only by atropine and not by propanolol or phentolamine. In addition to the above effects, carbachol also caused a rapid increase in the parotid guanosine-3', 5' cyclic monophosphate (cGMP) levels without a discernable effect on adenosine-3',5' cyclic monophosphate (cAMP) levels. The increase in cGMP level caused by carbachol was blocked by atropine and not by phentolamine. The stimulatory effect of carbachol on amylase release was not additive with that of isoproterenol or dibutyryl cAMP. Although carbachol had no effect on basal cAMP levels it did inhibit increases in cAMP caused by isoproterenol. Similarly isoproterenol inhibited increased in parotid cGMP levels caused by carbachol. Unlike the apparent nonadditivity between the effects of isoproterenol and carbachol on amylase release and cAMP and cGMP accumulation, the effects on K+ efflux were additive. The possibility of a role for cGMP in mediating the effects of cholinergic agonists on K+ efflux was lessened by our observations that 1-methyl-3-isobutylxanthine enhanced the effect of limiting concentrations of carbachol on cGMP accumulation while not enhancing the effects of carbachol on K+ efflux.
Mol Cell Endocrinol
PMID:Cholinergic regulation of cyclic nucleotide levels, amylase release, and K+ efflux from rat parotid glands. 18 78

In this work the kinetics of activation of the cyclic AMP-dependent protein kinase by several catecholamines and ACTH, have been studied in rat epididymal fat pads and isolated fat cells. The method of Soderling and co-workers which permits the measurement of the state of activation of the protein kinase after hormonal stimulation in adipose tissue, has been used. Kinetics experiments where norepinephrine was used showed that the results obtained with isolated cells conform to the models of Sutherland and Brostrom and co-workers. Wtih intact tissue, norepinephrine not only stimulates the protein kinase activity measured without exogenous cyclic AMP but also the total activity measured in the presence of cyclic AMP (5 X 10(-6) M); thus the effect of norepinephrine, obtained during incubation of the tissue, and that of cyclic AMP, added to the soluble fraction after incubation, were additive. This effect seems to be of the beta type because it is blocked completely by propranolol. A weak, additive but significant effect was also obtained with epinephrine and isoproterenol but not with ACTH. Neither cyclic GMP nor cyclic IMP seems implicated in this effect. It was shown that stroma vascular cells which are present in the fat pads are not involved. These results suggest that the effects of norepinephrine on the protein kinase of the fat pads cannot be completely explained by the model of Brostrom and colleagues.
Mol Cell Endocrinol 1976 Oct
PMID:Additive effects of norepinephrine and cyclic AMP on the activation of the protein kinase from adipose tissue. 18 9

The expression of cell cycle events in Caulobacter crescentus CB13 has been shown to be associated with regulation of carbohydrate utilization. Growth on lactose and galactose depends on induction of specific enzymes. Prior growth on glucose results in a delay in enzyme expression and cell cycle arrest at the nonmotile, predivisional stage. Dibutyryl cyclic adenosine 3',5'-monophosphate (AMP) was shown to stimulate expression of the inducible enzymes and, thus, the initiation of the cell cycle. beta-Galactosidase-constitutive mutants did not exhibit a cell cycle arrest upon transfer of cultures from glucose to lactose. Furthermore, carbon source starvation results in accumulation of the cells at the predivisional stage. The cell cycle arrest therefore results from nutritional deprivation and is analogous to the general control system exhibited by yeast (Hartwell, Bacteriol. Rev. 38:164-198, 1974; Wolfner et al., J. Mol. Biol. 96:273-290, 1975), which coordinates cell cycle initiation with metabolic state. Transfer of C. crescentus CB13 from glucose to mannose did not result in a cell cycle arrest, and it was demonstrated that this carbon source is metabolized by constitutive enzymes. Growth on mannose, however, is stimulated by exogenous dibutyryl cyclic AMP without a concomitant increase in the specific activity of the mannose catabolic enzymes. The effect of cyclic AMP on growth on sugars metabolized by inducible enzymes, as well as on sugars metabolized by constitutive enzymes, may represent a regulatory system common to both types of sugar utilization, since they share features that differ from glucose utilization, namely, temperature-sensitive growth and low intracellular concentrations of cyclic guanosine 3',5'-monophosphate.
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PMID:Effect of carbon source and the role of cyclic adenosine 3',5'-monophosphate on the Caulobacter cell cycle. 19 60

Preparations of human erythrocyte membranes have been made which are in the form of sealed vesicles and which behave as osmometers on suspension in solutions of simple inorganic salts. Using these preparations the permeability of the membranes to Na+, K+, Mg2+ and Ca2+ was measured. Cyclic AMP (but not cyclic GMP) increased the permeability of the membranes to Ca2+ with a half maximal effect at a concentration of 25 microgram but did not affect the permeability to the other ions tested. Phosphorylation of proteins in the erthrocyte membrane lowered the permeability to Ca2+ without affecting the permeability to the other ions tested and there was a good correlation between the time course of protein phosphorylation and decrease in Ca2+ permeability. It is postulated that the system through which cyclic AMP causes an initial rapid rise in Ca2+ permeability followed by increased phosphorylation of membrane proteins and reduced Ca2+ permeability may have a widespread occurrence in biological systems and serve to control the concentration of Ca2+ in the cytoplasm.
Mol Cell Biochem 1978 Jun 28
PMID:The effect of cyclic nucleotides and protein phosphorylation on the permeability of human erythrocyte ghosts to certain cations. 20 14

DEAE-Sephadex chromatography reveals the presence in extracts of human bronchial tissue of at least three separate cyclic nucleotide phosphodiesterases: a cyclic GMP-specific high affinity enzyme, a non-specific low affinity enzyme, and a high affinity cyclic AMP-specific enzyme. The activity of each fraction was partially characterized with respect to kinetic parameters, thermal stability, and the influence of a number of inhibitors. Each activity was found to resemble the activity of the previously characterized corresponding enzyme from whole lung tissue extracts. A high affinity non-specific phospho-diesterase previously isolated from lung tissue is missing in extracts of bronchial tissue.
Mol Cell Biochem 1978 Oct 13
PMID:Partial purification and characterization of cyclic nucleotide phosphodiesterases from human bronchial tissue. 21 99

The dependency of the oestrogen-induced increase in uterine cGMP content towards the cytosol-nuclear receptor system was investigated. The following observations were made: (1) With oestradiol-17 beta (E2-17 beta), U11-100A (UA) or CI-628 (CI) the cGMP response elicited in the uterus of immature rats followed a course that was parallel to (yet delayed by about 1 h from it) the known time-course evolution of nuclear occupancy by the complex formed by each compound with the oestrogen-receptor. (2) While a marked (about 2-fold) increase in uterine cGMP content was obtained with 0.1 microgram E2-17 beta, oestradiol-17 alpha (E2-17 alpha) given at the same dose had no effect on uterine cGMP. (3) The 2--3 h response to E2-17 beta (or to UA) could not be obtained in animals that had received a first injection of E2-17 beta, 2 h, or of one of the anti-oestrogens UA or tamoxifen, 20--22 h prior to the test injection of E2-17 beta. Those 3 treatments have in common that, at the time indicated, they create a state of depletion in the uterine cytosolic receptor population. The cGMP response to E2-17 beta was restored 20--22 h following a first injection of E2-17 beta. This time is known, in this case, to correspond to full replenishment of the cytosol-receptor population. In all those tests, the wet weight increase, measured in the same organs, behaves exactly as did the cGMP response. These results support the conclusion that the increase in uterine cGMP after oestrogen administration to the immature rat, represents a true hormonal action which, like other uterotrophic actions of oestrogens, involves binding of the hormone by the cytosol receptor.
Mol Cell Endocrinol 1979 Mar
PMID:Oestrogen-induced increase in uterine cGMP content: a true hormonal action? 22 Dec 91

Carbamylcholine and acetylcholine through a muscarinic type of receptor, KCl, ionophore A-23187 and NaF increased cyclic GMP accumulation in dog-thyroid slices. These effects were abolished in calcium-depleted slices, which findings confirm that Ca2+ is required for cyclic GMP accumulation. All these agents depressed the accumulation of cyclic AMP in TSH-stimulated slices. KCl and NaF depressed cyclic AMP accumulation in TSH-treated slices even when they had been depleted of Ca2+. This suggests a cyclic GMP- and Ca2+-independent mechanism. The absence of inhibition of the effects of the ionophore, NaF and KCl in the presence of atropine suggests that these drugs do not act by inducing the release of acetylcholine in the slices. The effects of carbamylcholine and ionophore A-23187 on cyclic GMP accumulation and protein iodination were reversible; the inhibitions of TSH-induced cyclic AMP accumulation and secretion were non-competitive and were not accompanied by a depression of ATP levels. All these effects were greatly decreased in the absence of extracellular Ca2+. These data suggest that carbamylcholine and ionophore A-23187 act mainly by increasing the influx of extracellular Ca2+ in thyroid cells. However, the persistence of some carbamylcholine effect in the absence of Ca2+ in the medium suggests that this agent may also trigger the release of Ca2+ from an intrafollicular pool. The kinetics of action of carbamylcholine are compatible with a role of cyclic GMP in the inhibition of cyclic AMP accumulation. However, with the ionophore, the depression of cyclic AMP accumulation was much longer than the rise of cyclic GMP, which suggests a mechanism independent of cyclic GMP.
Mol Cell Endocrinol 1979 Apr
PMID:Effects of carbamylcholine and ionophore A-23187 on cyclic 3',5'-AMP and cyclic 3',5'-GMP accumulation in dog-thyroid slices. 22 40


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