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

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.

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Bicarbonate Evokes Reciprocal Changes in Intracellular Cyclic di-GMP and Cyclic AMP Levels in Pseudomonas aeruginosa

Biology ◽

10.3390/biology10060519 ◽

2021 ◽

Vol 10 (6) ◽

pp. 519

Author(s):

Kasidid Ruksakiet ◽

Balázs Stercz ◽

Gergő Tóth ◽

Pongsiri Jaikumpun ◽

Ilona Gróf ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Cyclic Amp ◽

Biofilm Formation ◽

Second Messengers ◽

Brain Heart Infusion ◽

Ambient Air ◽

Dependent Manner ◽

Environmental Signals ◽

Common Causes ◽

Camp Levels

The formation of Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) is one of the most common causes of morbidity and mortality in CF patients. Cyclic di-GMP and cyclic AMP are second messengers regulating the bacterial lifestyle transition in response to environmental signals. We aimed to investigate the effects of extracellular pH and bicarbonate on intracellular c-di-GMP and cAMP levels, and on biofilm formation. P. aeruginosa was inoculated in a brain–heart infusion medium supplemented with 25 and 50 mM NaCl in ambient air (pH adjusted to 7.4 and 7.7 respectively), or with 25 and 50 mM NaHCO3 in 5% CO2 (pH 7.4 and 7.7). After 16 h incubation, c-di-GMP and cAMP were extracted and their concentrations determined. Biofilm formation was investigated using an xCelligence real-time cell analyzer and by crystal violet assay. Our results show that HCO3− exposure decreased c-di-GMP and increased cAMP levels in a dose-dependent manner. Biofilm formation was also reduced after 48 h exposure to HCO3−. The reciprocal changes in second messenger concentrations were not influenced by changes in medium pH or osmolality. These findings indicate that HCO3− per se modulates the levels of c-di-GMP and cAMP, thereby inhibiting biofilm formation and promoting the planktonic lifestyle of the bacteria.

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Biochemical parameters regulating forward motility initiation in vitro in goat immature epididymal spermatozoa

Reproduction Fertility and Development ◽

10.1071/r98003 ◽

1998 ◽

Vol 10 (4) ◽

pp. 299 ◽

Cited By ~ 18

Author(s):

Bijay S. Jaiswal ◽

Gopal C. Majumder

Keyword(s):

Cyclic Amp ◽

Sperm Motility ◽

Biochemical Parameters ◽

Vital Role ◽

Dependent Manner ◽

Alkaline Ph ◽

Heat Stable ◽

Heat Stable Protein ◽

Dose Dependent

An investigation was carried out to analyse the biochemical parameters influencing forward motility (FM) initiation in vitro in the goat caput-epididymal immature spermatozoa. Forward motility was induced in approximately 55% of caput-sperm upon incubation in an alkaline (pH 8.0) modified Ringer’s solution containing theophylline (30 mM) (an inhibitor of cyclic AMP phosphodiesterase), dialysed epi-didymal plasma (EP) and bicarbonate. Both EP and bicarbonate induced sperm motility in a dose-dependent manner, and at saturating doses EP (0.6 mg protein mL–1) and bicarbonate (25 mM) induced FM in approx-imately 38% and 44% of the cells, respectively. The motility-promoting efficacy of EP was attributed to a heat-stable protein termed ‘forward motility protein’ (FMP). Bicarbonate served as an initiator as well as a stabilizer of FM and its action was not dependent on FMP. FMP can induce FM in the caput-sperm, but it is not essential for sperm motility initiation. Alteration of the medium pH from 6.60 to 8.00 caused a marked increase in the EP or bicarbonate-dependent sperm FM initiation, as well as intrasperm pH. At the physio-logical pH, bicarbonate served as a much more potent motility activator than FMP, although both the motility promoters showed maximal efficacy at alkaline pH (~7.8). EP as well as bicarbonate elevated the intrasperm cyclic AMP level. Unlike EP, bicarbonate is capable of increasing intrasperm pH. The intrasperm pH increased from 6.54 0.02 to 6.77 0.03 during sperm transit from caput to cauda. The data are con-sistent with the view that FMP activates sperm forward motility by enhancing the intrasperm cyclic AMP level and that extracellular bicarbonate and pH play a vital role in the initiation of sperm FM during the epi-didymal transit.

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Cross-talk between glucagon- and adenosine-mediated signalling systems in rat hepatocytes: effects on cyclic AMP-phosphodiesterase activity

Biochemical Journal ◽

10.1042/bj3120763 ◽

1995 ◽

Vol 312 (3) ◽

pp. 763-767 ◽

Cited By ~ 14

Author(s):

M Robles-Flores ◽

G Allende ◽

E Piña ◽

J A García-Sáinz

Keyword(s):

Cyclic Amp ◽

Pertussis Toxin ◽

Plasma Membranes ◽

Rat Hepatocytes ◽

Dependent Manner ◽

Phosphodiesterase Activity ◽

Cyclic Amp Phosphodiesterase ◽

Cyclic Amp Accumulation ◽

A1 Adenosine Receptors ◽

Dose Dependent

The effect of adenosine analogues on glucagon-stimulated cyclic AMP accumulation in rat hepatocytes was explored. N6-Cyclopentyladenosine (CPA), 5′-N-ethylcarboxamidoadenosine and N6-(R-phenylisopropyl)adenosine inhibited in a dose-dependent manner the cyclic AMP accumulation induced by glucagon. This effect seems to be mediated through A1 adenosine receptors. Pertussis toxin completely abolished the effect of CPA on glucagon-stimulated cyclic AMP accumulation in whole cells which suggested that a pertussis-toxin-sensitive G-protein was involved. On the other hand, this action of adenosine analogues on glucagon-induced cyclic AMP accumulation was reverted by the selective low-Km cyclic AMP-phosphodiesterase inhibitor Ro 20-1724. Analysis of cyclic AMP-phosphodiesterase activity in purified hepatocyte plasma membranes showed that glucagon in the presence of GTP inhibited basal PDE activity by 45% and that CPA reverted this inhibition in dose-dependent manner. In membranes derived from pertussis-toxin-treated rats, we observed no inhibition of cyclic AMP-phosphodiesterase activity by glucagon in the absence or presence of CPA. Our results indicate that in hepatocyte plasma membranes, stimulation of adenylate cyclase activity and inhibition of a low-Km cyclic AMP phosphodiesterase activity are co-ordinately regulated by glucagon, and that A1 adenosine receptors can inhibit glucagon-stimulated cyclic AMP accumulation by blocking glucagon's effect on phosphodiesterase activity.

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Studies of esterase 6 in Drosophila melanogaster: XI. Modification of esterase 6 activity by unlinked genes

Genetics Research ◽

10.1017/s0016672300018991 ◽

1982 ◽

Vol 40 (2) ◽

pp. 109-125 ◽

Cited By ~ 12

Author(s):

Craig S. Tepper ◽

Rollin C. Richmond ◽

Anne L. Terry ◽

Alayne Senior

Keyword(s):

Drosophila Melanogaster ◽

Structural Gene ◽

Specific Activity ◽

Allelic Variation ◽

Regulatory Gene ◽

Natural Populations ◽

Gene Products ◽

Gene Variation ◽

Esterase 6 ◽

Regulatory Loci

SUMMARYThe often remarkable similarity in structural gene products among related species has led to the hypothesis that species differences may reside largely in changes at regulatory gene loci. This hypothesis assumes that groups capable of speciating have allelic variation at regulatory loci in their natural populations. We have undertaken an analysis of the mode of regulation of the esterase 6 (Est 6) locus in Drosophila melanogaster to determine the nature and extent of regulatory gene variation in natural populations. Analyses of esterase 6 (EST 6) activity among strains carrying the same thermostability variants reveal that significant, specific-activity differences are present. Reciprocal crosses between lines having high and low EST 6 activity show that loci other than the Est 6 structural gene influence EST 6 activity. Analyses of male hybrids from crosses between D. melanogaster and simulans indicate that the X chromosome of these flies affects the expression of the Est 6 locus, resulting in unequal levels of enzyme activity from the two alleles. The effect is sex and tissue specific. Female hybrids carrying the X chromosomes of both species exhibit equal expression of the two Est 6 alleles. We have determined whether natural populations are polymorphic for X chromosomes which affect EST 6 activity by extracting single X chromosomes from wild-collected males and placing these chromosomes in identical genetic backgrounds. Stocks which are otherwise genetically identical but carry independently derived X chromosomes show significant differences in the activity of EST 6. These data suggest that regulatory loci may be commonly polymorphic in natural populations.

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

Biochemistry and Cell Biology ◽

10.1139/o96-072 ◽

1996 ◽

Vol 74 (5) ◽

pp. 669-674 ◽

Cited By ~ 18

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

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Defect in cyclic AMP phosphodiesterase due to the dunce mutation of learning in Drosophila melanogaster

Nature ◽

10.1038/289079a0 ◽

1981 ◽

Vol 289 (5793) ◽

pp. 79-81 ◽

Cited By ~ 254

Author(s):

Duncan Byers ◽

Ronald L. Davis ◽

John A. Kiger

Keyword(s):

Drosophila Melanogaster ◽

Cyclic Amp ◽

Cyclic Amp Phosphodiesterase

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Increase in Endogenous and Exogenous Cyclic AMP Levels Inhibits Sclerotial Development in Sclerotinia sclerotiorum

Applied and Environmental Microbiology ◽

10.1128/aem.64.7.2539-2544.1998 ◽

1998 ◽

Vol 64 (7) ◽

pp. 2539-2544 ◽

Cited By ~ 54

Author(s):

Jeffrey A. Rollins ◽

Martin B. Dickman

Keyword(s):

Cyclic Amp ◽

Sclerotinia Sclerotiorum ◽

Growth And Development ◽

Mycelial Growth ◽

Dependent Manner ◽

Wild Type ◽

Concentration Dependent Manner ◽

Sclerotial Development ◽

Camp Levels ◽

Methyl Xanthine

ABSTRACT Growth and development of a wild-type Sclerotinia sclerotiorum isolate were examined in the presence of various pharmacological compounds to investigate signal transduction pathways that influence the development of sclerotia. Compounds known to increase endogenous cyclic AMP (cAMP) levels in other organisms by inhibiting phosphodiesterase activity (caffeine and 3-isobutyl-1-methyl xanthine) or by activating adenylate cyclase (NaF) reduced or eliminated sclerotial development in S. sclerotiorum. Growth in the presence of 5 mM caffeine correlated with increased levels of endogenous cAMP in mycelia. In addition, incorporation of cAMP into the growth medium decreased or eliminated the production of sclerotia in a concentration-dependent manner and increased the accumulation of oxalic acid. Inhibition of sclerotial development was cAMP specific, as exogenous cyclic GMP, AMP, and ATP did not influence sclerotial development. Transfer of developing cultures to cAMP-containing medium at successive time points demonstrated that cAMP inhibits development prior to or during sclerotial initiation. Together, these results indicate that cAMP plays a role in the early transition between mycelial growth and sclerotial development.

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The Effect of Mitomycin C on Platelet Aggregation and Adenosine 3′, 5′-Monophosphate Metabolism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646667 ◽

1978 ◽

Vol 39 (01) ◽

pp. 177-185 ◽

Cited By ~ 3

Author(s):

Shuichi Hashimoto ◽

Sachiko Shibata ◽

Bonro Kobayashi

Keyword(s):

Platelet Aggregation ◽

Cyclic Amp ◽

Mitomycin C ◽

Blood Platelets ◽

Adenosine Diphosphate ◽

Cellular Membrane ◽

Adenyl Cyclase ◽

Cyclic Amp Phosphodiesterase ◽

Membrane Structure And Function ◽

And Function

SummaryThe effect of Mitomycin C on aggregation, adenosine 3′, 5′-monophosphate (cyclic AMP) metabolism and reactions induced by thrombin was studied in rabbit platelets. Mitomycin C inhibited the platelet aggregation induced by adenosine diphosphate or thrombin. The level of radioactive cyclic AMP derived from 8-14C adenine or 8-14C adenosine increased after incubating intact platelets with Mitomycin G. Formation of radioactive adenosine triphosphate also increased though mitochondrial oxidation was not stimulated. Similar effect was observed also in rabbit liver. Mitomycin C failed to stimulate platelet adenyl cyclase but inhibited cyclic AMP phosphodiesterase in the absence of theophylline. In the platelets preincubated with Mitomycin C, thrombin-induced inhibition of adenyl cyclase, stimulation of membrane-bound cyclic AMP phosphodiesterase, and release of 250,000 dalton protein from platelet membranes were prevented. These results suggest that Mitomycin C will affect cellular membrane structure and function, and this extranuclear effect of Mitomycin C will lead to inhibition of aggregation in blood platelets.

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Cyclic AMP phosphodiesterase in diabetes. Effect of glyburide

Diabetes ◽

10.2337/diabetes.35.11.1233 ◽

1986 ◽

Vol 35 (11) ◽

pp. 1233-1236 ◽

Cited By ~ 6

Author(s):

S. S. Solomon ◽

J. Deaton ◽

T. P. Shankar ◽

M. Palazzolo

Keyword(s):

Cyclic Amp ◽

Cyclic Amp Phosphodiesterase

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The Biological Effects of Forsythia Leaves Containing the Cyclic AMP Phosphodiesterase 4 Inhibitor Phillyrin

Molecules ◽

10.3390/molecules26082362 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2362

Author(s):

Sansei Nishibe ◽

Kumiko Mitsui-Saitoh ◽

Junichi Sakai ◽

Takahiko Fujikawa

Keyword(s):

Cyclic Amp ◽

Influenza A ◽

Biological Effects ◽

Polyphenolic Compounds ◽

Pde4 Inhibitor ◽

Food Material ◽

Common Component ◽

Phosphodiesterase 4 ◽

Cyclic Amp Phosphodiesterase ◽

Forsythia Suspensa

Forsythia fruit (Forsythia suspensa Vahl (Oleaceae)) is a common component of Kampo medicines for treating the common cold, influenza, and allergies. The main polyphenolic compounds in the leaves of F. suspensa are pinoresinol β-d-glucoside, phillyrin and forsythiaside, and their levels are higher in the leaves of the plant than in the fruit. It is known that polyphenolic compounds stimulate lipid catabolism in the liver and suppress dyslipidemia, thereby attenuating diet-induced obesity and polyphenolic anti-oxidants might attenuate obesity in animals consuming high-fat diets. Recently, phillyrin was reported as a novel cyclic AMP phosphodiesterase 4 (PDE4) inhibitor derived from forsythia fruit. It was expected that the leaves of F. suspensa might display anti-obesity effects and serve as a health food material. In this review, we summarized our studies on the biological effects of forsythia leaves containing phillyrin and other polyphenolic compounds, particularly against obesity, atopic dermatitis, and influenza A virus infection, and its potential as a phytoestrogen.

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