Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preservation of human semen in liquid nitrogen causes a significant impairment of sperm motility. Ejaculated human spermatozoa show an increased motility in the presence of caffeine, a phosphodiesterase inhibitor, and pancreatic kallikrein (EC 3.4.21.8), a kinin-producing proteinase. Hence, the effect of both substances on post-thaw motility, fructose consumption, and cervical mucus penetration of cryo-preserved human spermatozoa was investigated. The results indicate that both substances stimulate the motility of freshly ejaculated spermatozoa and also improve the motility pattern of cryo-preserved human spermatozoa, thus offering a possible means of improving the quality of freeze-preserved human semen.
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PMID:Effect of caffeine and kallikrein on cryo-preserved human spermatozoa. 3 76

Phosphodiesterase is shown to occur in ram semen, and its activity to be higher in spermatozoa than in seminal plasma. Using similar substrate levels, the rate at which adenosine 3',5'-monophosphate (cyclic AMP) is metabolized by phosphodiesterase in spermatozoa is about 100 times higher than that of cyclic AMP synthesis by adenylate cyclase. In spermatozoa, phosphodiesterase is present partly in a soluble form, and partly bound; both forms can be extracted by sonication. The soluble enzyme (pH optimum 8-0, Km = 1-5 muM, mol. wt 165,000) occurs as a single isoenzyme, as shown by polyacrylamide gel electrophoresis and anion-exchange chromatography; this isoenzyme appears to be specific for spermatozoa and its formation in the testis coincides with the appearance of spermatozoa. The bound sperm enzyme has been solubilized with Trion X-100; it is a single isoenzyme (pH optimum 8-0, mol. wt 165,000) which is electrophoretically different from the soluble form, but similar to the phosphodiesterase found in other tissues. Seminal plasma phosphodiesterase (pH optimum 8-8, mol. wt 165,000) is present in the form of three isoenzymes; all three are different from the two forms of sperm phosphodiesterase, but are similar to the isoenzymes found in certain male accessory organs.
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PMID:Investigations on adenosine 3',5'-monophosphate phosphodiesterase in ram semen and initial characterization of a sperm-specific isoenzyme. 17 69

The cyclic AMP-phosphodiesterase (EC 3.1.4.17) of buffalo spermatozoa is distributed in the head, mid-piece and tail fractions and has multiple forms, 70% of which is in the bound form. The bound enzyme was not solubilized by Triton X-100, lubrol or hyamine 2389. Kinetic measurements of the soluble enzyme showed two apparent Km values for low and high cAMP concentrations, i.e. 4.5 and 100 micro M with Vmax values of 0.25 and 2.0 nmol cAMP hydrolysed min-1 mg protein-1. The bound enzyme had an apparent Km of 66.6 microM with a Vmax of 0.75 nmol cAMP hydrolysed min-1 mg protein-1. The pH for optimum enzyme activity was 7.5 and Mg2+ was essential for the activity of the soluble and bound enzymes. Methylxanthines, ATP, ADP and ppi inhibited the soluble and bound enzymes, ATP being the most potent inhibitor.
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PMID:Adenosine 3'5'-monophosphate phosphodiesterase of buffalo spermatozoa. 22 88

The lysosomal stabilizer and anti-malarial agent, chloroquine, stimulated the respiration and motility of fresh and aged bovine spermatozoa stored in vitro. Duplication of these effects by the phosphodiesterase inhibitors, theophylline and caffeine, suggested that enhancement of sperm activity by chloroquine may be mediated by cyclic AMP.
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PMID:Stimulatory effect of the lysosomal stabilizer, chloroquine, on the respiration and motility of fresh and aged bovine spermatozoa. 118 15

Four cAMP phosphodiesterase (cAMP-PDE) genes (ratPDE1, ratPDE2, ratPDE3, and ratPDE4) are expressed in the rat testis (Swinnen et al., PNAS USA 1989; 86:5325). Since multiple ratPDE1 and ratPDE2 mRNAs were present in male germ cells, their developmental expression was investigated by using purified spermatogenic cell populations. RatPDE1 mRNAs (4.0 and 2.8 kb) were found to be abundant in pachytene spermatocytes. RatPDE1 mRNA levels were decreased in round spermatids and absent from condensing spermatids/residual bodies. However, multiple ratPDE2 mRNAs (4.0, 3.5, 3.1, 2.8, and 2.4 kb) were abundant in round spermatids, and lower amounts were present in condensing spermatids/residual bodies. Transcripts related to ratPDE2 were also present in mouse round spermatids. Chromatography of germ cell cytosol identified two peaks of cAMP-PDE activity. Whereas peak A was evident in all germ cell populations examined, peak B was present in pachytene spermatocytes and round spermatids, but was at the limit of detection in condensing spermatids/residual bodies. The large decrease in peak B activity in condensing spermatids/residual bodies may be related to the drop in ratPDE1 mRNA levels observed during spermatogenesis. The sustained peak A activity in condensing spermatids/residual bodies coincides with the presence of ratPDE2 mRNA in these cells and suggests that the ratPDE2 enzyme may function during spermiogenesis and in spermatozoa.
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PMID:Unique adenosine 3',5' cyclic monophosphate phosphodiesterase messenger ribonucleic acids in rat spermatogenic cells: evidence for differential gene expression during spermatogenesis. 132 99

Preliminary evidence has suggested that the phosphodiesterase inhibitor pentoxifylline augments the fertilizing potential of asthenozoospermic sperm samples, presumably by improving sperm movement. Here, we used computer-assisted sperm movement analysis to compare the effects of pentoxifylline in normozoospermic and asthenozoospermic specimens. The study focused on the following issues: the changes in individual movement characteristics in response to pentoxifylline, the rapidity of the response, the effect of sperm capacitation on the response, the persistence of the response after drug removal and the variability of responses among asthenozoospermic individuals. Data obtained show that (i) pentoxifylline increases the curvilinear velocity, path velocity, straight-line velocity, lateral head displacement, beat cross frequency and sperm hyperactivation in both normozoospermic and asthenozoospermic specimens, (ii) pentoxifylline does not modify the percentage of motile spermatozoa, (iii) the pentoxifylline effect reaches a maximum within 10 min of treatment in fresh semen as well as in capacitated sperm suspensions and persists for at least 2 h after drug removal and (iv) pentoxifylline improves the movement characteristics in most asthenozoospermic individuals. Results are discussed with regard to methods of therapeutic application of pentoxifylline as an enhancer of sperm movement in assisted reproductive technology.
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PMID:Effect of pentoxifylline on sperm movement characteristics in normozoospermic and asthenozoospermic specimens. 147 8

The acrosome reaction of spermatozoa appears to be analogous to various somatic cell exocytotic events which involve cascade reactions, i.e., transmission of an external signal across the cell membrane resulting in activation of an "amplifier" enzyme and the generation of a second messenger. Using a synchronous acrosome reaction system (De Jonge et al., J. Androl., 10:232-239, '89a), it was found that analogues of the second-messenger cAMP, dibutyryl cAMP (dbcAMP) and 8-bromo cAMP, stimulated the acrosome reaction of capacitated spermatozoa. Additionally, treatment of spermatozoa with either xanthine or non-xanthine phosphodiesterase inhibitors induced a significant (P less than 0.05) increase in the percent acrosome reaction after a period of capacitation in comparison to untreated controls. These results indicate that analogues of cAMP or inhibitors which prevent cAMP hydrolysis can induce the human sperm acrosome reaction. Subsequent experiments were conducted to test whether the amplifier enzyme in the cascade reaction, adenylate cyclase, has a role in the acrosome reaction. Forskolin, an adenylate cyclase stimulator, caused a significant (P less than 0.01) increase in the percent acrosome reaction in comparison to controls. Modulators of adenylate cyclase--adenosine, 2'-0-methyladenosine, and 2',3'-dideoxyadenosine--significantly (P less than 0.01) inhibited the forskolin-induced acrosome reaction. dbcAMP was able to overcome the inhibition by adenosine. Two inhibitors of protein kinase A, the Walsh inhibitor and H-8, caused a significant (P less than 0.01) inhibition of the dbcAMP-induced acrosome reaction. Finally, in the absence of extracellular calcium, dbcAMP induced a significant (P less than 0.01) increase in the acrosome reaction in contrast to A23187. These results suggest that: 1) a molecular mechanism for the human sperm acrosome reaction involves the cAMP second-messenger system; i.e., activation of adenylate cyclase, the amplifier enzyme that produces cAMP, production of cAMP as a second messenger, and activation of cAMP-dependent kinase A; and that 2) activation of adenylate cyclase occurs after calcium influx.
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PMID:Modulation of the human sperm acrosome reaction by effectors of the adenylate cyclase/cyclic AMP second-messenger pathway. 165 65

Previous studies from this laboratory and others have identified several enzymes on the surface of mammalian spermatozoa. Some of these enzymes, namely a galactosyltransferase and a novel alpha-D-mannosidase, are believed to play a ligand-like role in recognizing and binding to the complementary moiety(ies) present on zona pellucida glycoconjugates. However, little or no information is available about the occurrence of these enzymes in human spermatozoa. In the present report, we show that a very small amount of the total galactosyltransferase activity present in human semen is associated with spermatozoa. Moreover, our failure to find a significant amount of the enzyme on sperm plasma membranes suggests that the enzyme is not associated with the sperm surface. Therefore, it is unlikely that galactosyltransferase in humans has the same ligand-like role in zona binding that is demonstrated in mouse sperm. In contrast, nearly 5% of alpha-D-mannosidase activity was repeatedly found in the salt-washed plasma membrane fraction. The recovery and enrichment of the alpha-D-mannosidase was nearly one-half that observed for adenylate cyclase and nearly one-third that for phosphodiesterase I, the two sperm plasma membrane marker enzymes. The differential enrichment and recovery of the sperm surface alpha-D-mannosidase is consistant with our previous studies in rat spermatozoa, and suggests that alpha-D-mannosidase may be localized on morphologically distinct region(s) of the sperm plasma membranes. The properties of human sperm surface alpha-D-mannosidase are quite similar to those reported by us for rat sperm plasma membrane mannosidase, but quite different from human sperm acid alpha-D-mannosidase. In addition, whereas anti-rat epididymal alpha-D-mannosidase antibody (IgG-fraction) cross-reacted with the human sperm acid alpha-D-mannosidase, no cross-reactivity was observed with the sperm surface mannosidase. A small amount of fucosyltransferase (less than 1% of the enzyme originally present on spermatozoa) was found in the salt-washed plasma membrane, but the enrichment of the enzyme was only one-tenth of that observed for adenylate cyclase. The potential ligand-like role of human sperm surface alpha-D-mannosidase and other sperm surface enzymes during fertilization is discussed.
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PMID:Human sperm plasma membranes possess alpha-D-mannosidase activity but no galactosyltransferase activity. 211 23

Phosphorylation of histone H1 occurs when spermatozoa of the sea urchin Strongylocentrotus purpuratus are treated with the macromolecular fraction of solubilized egg jelly. Phosphorylation is on serine residues in the N-terminal fragment of H1 bisected with N-bromosuccinimide. Phosphorylation is maximal by 4-8 min and dependent on Ca2+, but independent of Na+ or increased intracellular pH. Phosphorylation of H1 can be dissociated from the induction of the acrosome reaction. Only a fraction of the H1 molecules become phosphorylated upon treatment of sperm with egg jelly. The amount of phosphate per mole of H1 increases from 0.15 moles before jelly treatment to 0.46 moles after maximal phosphorylation. Phosphorylation of H1 occurs in a cAMP-dependent manner as indicated by the ability of the phosphodiesterase inhibitors IBMX and SQ20009 to induce H1 phosphorylation. This phosphorylation reaction can be blocked by digesting the sperm surface with Pronase, or preincubation of sperm in wheat germ agglutinin, showing that a ligand in egg jelly must interact with a sperm surface receptor to activate the kinase phosphorylating H1.
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PMID:Phosphorylation of sperm histone H1 is induced by the egg jelly layer in the sea urchin Strongylocentrotus purpuratus. 242 45

Exposure of cryostored human spermatozoa to 2-deoxyadenosine resulted in significant increases in percentage motility, the linear velocity of progression and the frequency of sperm head rotation, which were maximal at a dose of 2.5 mM. At the same dose both adenosine and caffeine significantly increased percentage motility, although neither compound influenced the quality of sperm movement as assessed by time-exposure photomicrography. 2-Deoxyadenosine was also significantly more effective than caffeine in sustaining the motility of cryostored spermatozoa as well as in enhancing the motility of fresh and washed preparations of human spermatozoa. The ability of caffeine and 2-deoxyadenosine to influence sperm motility was counteracted by the presence of calcium in the external medium although the latter was less susceptible to such inhibition and still enhanced motility in the presence of calcium levels (1.7 mM) typical of media used for in-vitro fertilization. The mechanism of action of 2-deoxyadenosine was associated with an increase of intracellular cAMP levels, which were sustained over a time course lasting from 5 to 180 min and exhibited significant dose dependency over the range 1-10 mM. The response to 2-deoxyadenosine did not involve any changes in the steady state levels of ATP and was augmented by the presence of the phosphodiesterase inhibitors, IBMX and caffeine. We conclude that 2-deoxyadenosine is a powerful stimulator of human sperm motility and that this effect involves an increase of intracellular cAMP levels via mechanisms which do not involve the classical 'R'-site receptor mediated pathway.
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PMID:Paradoxical stimulation of human sperm motility by 2-deoxyadenosine. 243 39


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