Cyclic AMP phosphodiesterase: a regulator of forward motility initiation during epididymal sperm maturation

1996 ◽  
Vol 74 (5) ◽  
pp. 669-674 ◽  
Author(s):  
Bijay S. Jaiswal ◽  
Gopal C. Majumder
Keyword(s):  
Cyclic Amp ◽  
Specific Inhibitor ◽  
Flagellar Motility ◽  
Epididymal Sperm ◽  
Camp Phosphodiesterase ◽  
Cyclic Amp Phosphodiesterase ◽  
Epididymal Maturation ◽  
Camp Levels ◽  
Sperm Maturity

The concentrations of cAMP, cAMP phosphodiesterase (PDE) activity, and the effect of theophylline in vitro on the forward motility (FM) of maturing goat epididymal sperm have been analyzed. cAMP levels increased slowly during transit of the cells from the caput to the proximal cauda, although they acquired a minimal degree of forward progression. The last phase of sperm transit (proximal to distal cauda) was associated with a concomitant sharp rise in the level of both c AMP as well as flagellar motility. PDE activity progressively decreased (approximately threefold) during epididymal maturation, being minimal in mature cauda sperm. Theophylline (30 mM), a specific inhibitor of PDE, markedly activated (10-fold or greater) motility of the sperm derived from proximal-corpus, mid-corpus, distal-corpus, and proximal-cauda epididymides. FM of the native mature caudal sperm was similar to that of the theophylline-treated proximal-cauda sperm. The terminal stage of sperm maturity (proximal to distal cauda) was associated with a markedly reduced level of theophylline-dependent motility activation (approximately 50%). The data are consistent with the view that PDE plays an important role in the initiation of motility during epididymal sperm maturation.Key words: epididymal sperm, cyclic AMP, cyclic AMP phosphodiesterase, flagellar motility, theophylline

scholarly journals A GENETICALLY DISTINCT FORM OF CYCLIC AMP PHOSPHODIESTERASE ASSOCIATED WITH CHROMOMERE 3D4 IN DROSOPHILA MELANOGASTER

Genetics ◽  
1979 ◽  
Vol 91 (3) ◽  
pp. 521-535
Author(s):  
John A Kiger ◽  
Eric Golanty
Keyword(s):  
Drosophila Melanogaster ◽  
Cyclic Amp ◽  
Structural Gene ◽  
Regulatory Gene ◽  
Heat Stability ◽  
Normal Female ◽  
Dependent Manner ◽  
Cyclic Amp Phosphodiesterase ◽  
Heat Stable ◽  
Camp Levels

ABSTRACT Two cyclic AMP phosphodiesterase enzymes (E.C.3.1.4.17) are present in homogenates of adult Drosophila melanogaster. The two enzymes differ from one another in heat stability, affinity for Mg++, Ca++ activation and molecular weight. They do not differ markedly in their affinities for cyclic AMP, and both exhibit anomalous Michaelis-Menten kinetics. The more heatlabile enzyme is controlled in a dosage-dependent manner by chromomere 3D4 of the X chromosome and is absent in flies that are deficient for chromomere 3D4. Chromomere 3D4 is also necessary for the maintenance of normal cAMP levels, for male fertility, and for normal female fertility and oogenesis. The structural gene(s) for the more heat-stable enzyme is located outside of chromomeres 3C12-3D4. Whether 3D4 contains a structural gene, or a regulatory gene necessary for the presence of the labile enzyme, remains to be determined.

Cloning and characterization of the low-affinity cyclic AMP phosphodiesterase gene of Saccharomyces cerevisiae

1987 ◽  
Vol 7 (10) ◽  
pp. 3629-3636
Author(s):  
J Nikawa ◽  
P Sass ◽  
M Wigler
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cyclic Amp ◽  
Copy Number ◽  
Growth Arrest ◽  
Yeast Cells ◽  
Phosphodiesterase Activity ◽  
Camp Phosphodiesterase ◽  
High Affinity ◽  
Cyclic Amp Phosphodiesterase

Saccharomyces cerevisiae contains two genes which encode cyclic AMP (cAMP) phosphodiesterase. We previously isolated and characterized PDE2, which encodes a high-affinity cAMP phosphodiesterase. We have now isolated the PDE1 gene of S. cerevisiae, which encodes a low-affinity cAMP phosphodiesterase. These two genes represent highly divergent branches in the evolution of phosphodiesterases. High-copy-number plasmids containing either PDE1 or PDE2 can reverse the growth arrest defects of yeast cells carrying the RAS2(Val-19) mutation. PDE1 and PDE2 appear to account for the aggregate cAMP phosphodiesterase activity of S. cerevisiae. Disruption of both PDE genes results in a phenotype which resembles that induced by the RAS2(Val-19) mutation. pde1- pde2- ras1- ras2- cells are viable.

scholarly journals Alteration of Platelet Cyclic AMP (cAMP) by Ethanol

1977 ◽  
Author(s):  
D.H. Cowan ◽  
M. Kikta ◽  
D. Baunach
Keyword(s):  
Cyclic Amp ◽  
Platelet Function ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Platelet Dysfunction ◽  
Camp Metabolism ◽  
Subnormal Level ◽  
Camp Levels ◽  
Stimulation Of

Studies of cAMP in human platelets exposed to ethanol were done to assess one possible mechanism for ethanol-related platelet dysfunction. Ingestion of ethanol by 3 subjects produced blood ethanol levels from 65-76 mM. Thrombocytopenia occurred in 1 subject and impaired platelet function occurred in all. Platelet cAMP decreased 36,51, and 59% below control levels. Infusion of ethanol to 2 normals produced blood ethanol levels of 43 mM and decreased platelet cAMP by 15% and 22%. Incubation of normal platelets with 86 mM ethanol in vitro decreased cAMP from 13.8 ± 2.9 (1 SD) to 9.4 ± 3.5 (p<0.02). By contrast, ethanol did not impair the increase in cAMP that occurred with 1.3 μM PGE1. Further, ethanol enhanced the increase in cAMP produced by 2.0 mM papaverine (Pap) by 160-220% and that produced by Pap + PGE1 by 58%. Dopamine, 0.1 mM, caused a 23% decrease in the basal level of cAMP, a 31% decrease below the subnormal level of cAMP seen with ethanol alone, and a 41% reduction in the increased level of cAMP produced by Pap + ethanol. The effect of ethanol on platelet cAMP metabolism is complex. Ethanol reduces basal levels of cAMP, does not decrease elevated levels that result from PGE1 stimulation of adenylate cyclase, and augments the inhibitory effect of Pap on platelet phosphodiesterase (PDE). Despite causing a decrease in basal cAMP levels, ethanol may impair platelet function by potentiating the effect of agents or other conditions which increase cAMP. The effect of ethanol on Pap-stimulated PDE activity may be blocked by dopamine, a neuropharmacologic agent that is actively accumulated by platelets.

scholarly journals Cyclic AMP Controls mTOR through Regulation of the Dynamic Interaction between Rheb and Phosphodiesterase 4D

2010 ◽  
Vol 30 (22) ◽  
pp. 5406-5420 ◽  
Author(s):  
Hyun Wook Kim ◽  
Sang Hoon Ha ◽  
Mi Nam Lee ◽  
Elaine Huston ◽  
Do-Hyung Kim ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Mammalian Target Of Rapamycin ◽  
Dynamic Interaction ◽  
Negative Regulator ◽  
Camp Phosphodiesterase ◽  
Extracellular Stimuli ◽  
Phosphodiesterase 4D ◽  
Signaling Components ◽  
Camp Levels ◽  
Regulatory Event

ABSTRACT The mammalian target of rapamycin complex 1 (mTORC1) is a molecular hub that regulates protein synthesis in response to a number of extracellular stimuli. Cyclic AMP (cAMP) is considered to be an important second messenger that controls mTOR; however, the signaling components of this pathway have not yet been elucidated. Here, we identify cAMP phosphodiesterase 4D (PDE4D) as a binding partner of Rheb that acts as a cAMP-specific negative regulator of mTORC1. Under basal conditions, PDE4D binds Rheb in a noncatalytic manner that does not require its cAMP-hydrolyzing activity and thereby inhibits the ability of Rheb to activate mTORC1. However, elevated cAMP levels disrupt the interaction of PDE4D with Rheb and increase the interaction between Rheb and mTOR. This enhanced Rheb-mTOR interaction induces the activation of mTORC1 and cap-dependent translation, a cellular function of mTORC1. Taken together, our results suggest a novel regulatory mechanism for mTORC1 in which the cAMP-determined dynamic interaction between Rheb and PDE4D provides a key, unique regulatory event. We also propose a new role for PDE4 as a molecular transducer for cAMP signaling.

The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans

Microbiology ◽  
2003 ◽  
Vol 149 (10) ◽  
pp. 2961-2976 ◽  
Author(s):  
Won Hee Jung ◽  
Lubomira I. Stateva
Keyword(s):  
Candida Albicans ◽  
Solid Medium ◽  
Camp Phosphodiesterase ◽  
Growth Defects ◽  
High Affinity ◽  
Lateral Buds ◽  
Camp Levels ◽  
Dependent Pathway ◽  
Higher Sensitivity

The cAMP-dependent pathway, which regulates yeast-to-hypha morphogenesis in Candida albicans, is controlled by changes in cAMP levels determined by the processes of synthesis and hydrolysis. Both low- and high-affinity cAMP phosphodiesterases are encoded in the C. albicans genome. CaPDE2, encoding the high-affinity cAMP phosphodiesterase, has been cloned and shown to be toxic in Saccharomyces cerevisiae upon overexpression under pGAL1, but functional under the moderate pMET3. Deletion of CaPDE2 causes elevated cAMP levels and responsiveness to exogenous cAMP, higher sensitivity to heat shock, severe growth defects at 42 °C and highly reduced levels of EFG1 transcription. In vitro in hypha-inducing liquid medium CaPDE2, deletion prohibits normal hyphal, but not pseudohyphal growth. On solid medium capde2 mutants form aberrant hyphae, with fewer branches and almost no lateral buds, which are deficient in hypha-to-yeast reversion. The phenotypic defects of capde2 mutants show that the cAMP-dependent pathway plays specific roles in hyphal and pseudohyphal development, its regulatory role however, being greater in liquid than on solid medium in vitro. The increased expression of CaPDE2 after serum addition correlates well with a drop in cAMP levels following the initial rise in response to the hyphal inducer. These results suggest that Capde2p mediates a desensitization mechanism by lowering basal cAMP levels in response to environmental stimuli in C. albicans.

Insulin inhibition of hormone-stimulated protein kinase systems of rat renal cortex.

1979 ◽  
Vol 236 (6) ◽  
pp. E649 ◽  
Author(s):  
T E Northrup ◽  
P A Krezowski ◽  
P J Palumbo ◽  
J K Kim ◽  
Y S Hui ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Renal Cortex ◽  
Fractional Excretion ◽  
Camp Phosphodiesterase ◽  
Kinase Activation ◽  
Protein Kinase Activation ◽  
Fractional Excretion Of Phosphate ◽  
Camp Levels

Parathyroid hormone (PTH) and glucagon increase the urinary fractional excretion of phosphate, but insulin administration is associated with a decreased fractional excretion of phosphate. It was the purpose of this study to determine whether insulin will antagonize the effects of PTH and glucagon on cAMP levels and protein kinase activation of rat renal cortex. In situ incubation studies were performed on rat renal cortical slices exposed to insulin, PTH, and glucagon. Insulin alone did not affect the tissue cAMP and cGMP levels or the state of protein kinase activation. Preincubation of slices with insulin, however, did significantly inhibit increases in protein kinase activation induced by both PTH and glucagon. Insulin also significantly inhibited PTH-stimulated increases in tissue cAMP levels, but did not blunt the elevations of cAMP levels induced by glucagon. Insulin (10(-9) M) had no effect on either the in vitro activity of adenylate cyclase, basal or PTH-stimulated, or on the activities of low Km cytosolic or membrane-bound cAMP phosphodiesterase. The data show that insulin antagonizes activation of protein kinase by both PTH and glucagon in renal cortex. Separate mechanisms are probably involved for PTH and glucagon interaction. The antiphosphaturic effect of insulin in vivo may result in part from this antagonism at the cellular level.

Cyclic AMP-phosphodiesterase induces dedifferentiation of prespore cells in Dictyostelium discoideum slugs: evidence that cyclic AMP is the morphogenetic signal for prespore differentiation

Development ◽  
1988 ◽  
Vol 103 (3) ◽  
pp. 611-618 ◽  
Author(s):  
M. Wang ◽  
R. van Driel ◽  
P. Schaap
Keyword(s):  
Cyclic Amp ◽  
Hydrolysis Product ◽  
Camp Level ◽  
Camp Phosphodiesterase ◽  
Multicellular Development ◽  
Local Reduction ◽  
Coated Spheres ◽  
Extracellular Camp ◽  
Camp Levels ◽  
General Reduction

We investigated whether cyclic AMP is an essential extracellular stimulus for the differentiation of prespore cells in slugs of D. discoideum. A local reduction of the extracellular cAMP level inside the slug was induced by implantation of cAMP-phosphodiesterase (cAMP-PDE)-coated spheres in intact slugs. This treatment caused the disappearance of prespore antigen in the vicinity of the sphere. A general reduction of extracellular cAMP levels in slugs, induced by submerging slugs in 0.25i.u.ml-1 cAMP-PDE, reduced the proportion of prespore cells from 66% to 15%, without affecting slug morphology. The cAMP-PDE-induced dedifferentiation of prespore cells was counteracted by cAMP and was not due to the production of the hydrolysis product 5′AMP, but to the reduction of extracellular cAMP levels. We conclude that extracellular cAMP is the major morphogenetic signal for the differentiation of prespore cells in the multicellular stages of D. discoideum development and we present a working hypothesis for the generation of the prestalk/prespore pattern during multicellular development.

Accumulation of Adenosine 3′,5′-Monophosphate and Relaxation in the Rat Uterus In Vitro

1971 ◽  
Vol 49 (11) ◽  
pp. 999-1004 ◽  
Author(s):  
Ivo Polacek ◽  
Jean Bolan ◽  
Edwin E. Daniel
Keyword(s):  
Cyclic Amp ◽  
Contractile Activity ◽  
Phosphodiesterase Activity ◽  
Dibutyryl Camp ◽  
Rat Uterus ◽  
Low Concentrations ◽  
Uterine Contractile ◽  
Camp Levels

Theophylline, diazoxide, and papaverine in low concentrations relaxed the uterus with minimal or no elevation of cyclic AMP (cAMP) levels. In higher concentrations, theophylline relaxed the uterus and increased its cAMP levels, but imidazole reversed the increase in cAMP without causing recontraction. Imidazole and NaF caused uterine contractures but did not detectably decrease cAMP levels until several minutes after the onset of contractures. The uterine relaxations produced by theophylline and/or dibutyryl cAMP in amounts which increased uterine cAMP were not reversed by propranolol. These results eliminate the possibility that propranolol interfered with a relaxant action of cAMP. Along with previous data, these results also show that uterine contractile activity was not determined primarily by the general levels of cAMP and that phosphodiesterase activity in the uterus was insufficient to rapidly affect these cAMP levels. Also, substances like theophylline, diazoxide, and papaverine, postulated to inhibit phosphodiesterase activity, did not bring about their relaxant effects by this mechanism.

scholarly journals Long-term effects of a high glucose concentration on cyclic nucleotide phosphodiesterase activity in mouse pancreatic islets maintained in tissue culture

1976 ◽  
Vol 156 (2) ◽  
pp. 461-463 ◽  
Author(s):  
C Berne ◽  
A Andersson
Keyword(s):  
Cyclic Amp ◽  
Pancreatic Islets ◽  
Glucose Concentration ◽  
Phosphodiesterase Activity ◽  
Long Term Effects ◽  
Isolated Pancreatic Islets ◽  
Cyclic Amp Phosphodiesterase ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose

It has been suggested that the stimulatory effect of glucose on insulin release may be mediated by the adenylate cyclase-cyclic AMP phosphodiesterase system. In this study it was found that exposure of isolated pancreatic islets to an elevated extracellular glucose concentration for 1 week in vitro caused an increase of the cyclic AMP phosphodiesterase activity in the islet cells. These and previous data indicate that there is an increased turnover of cyclic AMP in B-cells exposed for a prolonged time to a high extracellular glucose concentration, which also causes an increased turnover rate of insulin.

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