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)

In both Manduca sexta and Drosophila melanogaster, metamorphic events are driven by ecdysteroids whose production in prothoracic gland (PGs) is stimulated periodically by neural factors. Differences in the life cycle of moths and flies have made it difficult to compare the regulation of ecdysteroid biosynthesis in these two species. As in Manduca, at least two neural factors in the larval Drosophila BVG complex were separable by molecular weight, and they stimulated increased ecdysteroid biosynthesis from the ring gland, a composite organ that includes PG cells. Drosophila neural extracts accelerated ecdysteroid biosynthesis in Manduca PGs and, conversely, partially purified Manduca PTTH preparations elevated ecdysteroid biosynthesis in Drosophila ring glands, suggesting that the two species may share structurally similar prothoracicotropic factors. Drosophila ring glands required the presence of calcium ions to respond to neural extracts, but the phosphodiesterase inhibitor MIX and cAMP analogues exerted little, if any, positive effect on production. Mean ecdysteroid production rates of BVG-ring gland complexes taken from Drosophila larvae during various phases of the wandering period were often submaximal and highly variable, suggesting that they fluctuate widely prior to pupariation. Based on available data in Drosophila and the Manduca model for the control of ecdysteroid biosynthesis, a developmental scheme for neuroendocrine control in Drosophila is proposed.
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PMID:Comparison of ecdysteroid production in Drosophila and Manduca: pharmacology and cross-species neural reactivity. 757 74

Prothoracicotropic hormones (PTTHs) stimulate synthesis and secretion of ecdysteroids by insect prothoracic glands. In Manduca sexta, PTTH exists as two size variants, small and big PTTH. Experiments were performed to assess the possible role of cyclic AMP in small PTTH signal transduction. cAMP analogs, or agents that increase intracellular cAMP, stimulated ecdysteroidogenesis. Small PTTH enhanced glandular cAMP levels; the rise in cAMP preceded an increase in ecdysteroid secretion. Prothoracic glands accumulated less cAMP when treated with small PTTH than when treated with big PTTH. A phosphodiesterase inhibitor (1-methyl-3-isobutylxanthine) (MIX) increased the amount of cAMP in glands treated with small but not big PTTH, suggesting that glandular phosphodiesterase activity may be elevated in the presence of small PTTH. PTTH-stimulated ecdysteroid secretion was suppressed by a cAMP antagonist (Rp-cAMPS). The effects of small and big PTTH on ecdysteroidogenesis were non-additive. The combined results suggest that cAMP is employed as a second messenger by both prothoracicotropins, and that there may be subtle differences in their respective mechanisms of action.
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PMID:Stimulation of ecdysteroidogenesis by small prothoracicotropic hormone: role of cyclic AMP. 768 15

This study examined the potential role of testicular opioids, a pertussis toxin (PT)-sensitive G-protein, and phosphodiesterase in mediating the inhibitory effect of immobilization stress on testicular steroidogenesis in adult rats. The experiments were initiated with enriched preparations of Leydig cells, but the stress effect was not sustained in vitro either as a result of the disruption of the morphology of the testis and/or the time required for Leydig cell isolation. Consequently, testicular fragments from control and stressed (3-hour immobilization) rats were used in these experiments. When fragments from stressed rats were incubated for 2 hours in the absence and presence of human chorionic gonadotropin (hCG) (0.1,1, or 10 mlU), testosterone (T) production in response to 1 and 10 mlU hCG was lower (P < 0.05 and 0.01, respectively) than that from control fragments. Basal T secretion did not differ between stressed and control fragments. Naloxone (1, 10, or 100 mu M), did not alter basal or hCG-stimulated T secretion from control fragments, but it normalized the T response to hCG from stressed fragments. Control fragments also showed a reduced T response (P < 0.05) to hCG in the presence of beta-endorphin (beta-E; 36 nM). Incubation of control fragments with PT (30 ng) did not alter basal or hCG-stimulated T production. However, PT normalized (P < 0.01) hCG-stimulated T secretion from stressed fragments. Methylisobutylxanthine (MIX; 0.125 mM) elevated (P < 0.01) hCG-stimulated T production from control fragments, but hCG-stimulated T secretion from stressed fragments remained subnormal in the presence of the phosphodiesterase inhibitor. The data suggest that acute immobilization stress inhibits gonadotropin-induced T production in adult male rats via a mechanism involving testicular opioids and a PT sensitive G-protein. We found no evidence to suggest that a stress induced increase in the activity of phosphodiesterase was involved in this mechanism.
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PMID:Mechanism of stress-induced attenuation of the testicular response to gonadotropin: possible involvement of testicular opioids, a pertussis toxin-sensitive G-protein, and phosphodiesterase. 883 36

A potential role for cAMP in regulating the differentiation of myoblasts has led us to examine the components of the cAMP signaling system, including the type IV, cAMP-specific phosphodiesterases. The full coding sequence of the phosphodiesterase PDE4D1 was inserted in the bacterial expression vector pGEX-KG. N- and C-terminal truncations were also placed in the same vector, allowing the expression and purification of glutathione S-transferase (GST)-PDE fusion proteins using glutathione-Sepharose. The purified PDE was active [V(max) = 318 +/- 18 nmol min(-1)(mg of protein)(-1)] and inhibited by RO 20-1724, rolipram, and MIX (IC50 values of 2, 0.4, and 40 microM, respectively). The requirement of PDE4D1 for a divalent cation was also examined. It was able to use Mg2+, Co2+, and Mn2+, but not Zn2+, suggesting that it is not a zinc hydrolase as has been proposed for other PDE types. Deletion of both C- and N-terminal regions affected the apparent native size of the enzyme. The C-terminal region was involved in dimer formation, whereas an N-terminal region was responsible for larger aggregates. Removal of the last 35 amino acids of an N-terminal 80-residue highly conserved region (UCR2) resulted in a 6-fold increase in PDE activity, providing evidence that this part of the molecule acts as an intramolecular inhibitor. The availability of a highly purified, enzymatically active protein in substantial quantities has allowed us to directly examine PDE4D1 for the first time.
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PMID:Recombinant expression of a type IV, cAMP-specific phosphodiesterase: characterization and structure-function studies of deletion mutants. 906 27

The functional influence of cell proteoglycan (PG) undersulfation on estradiol synthesis by immature rat Sertoli cell cultures was investigated by using sodium chlorate, an inhibitor of the active sulfate donor for sulfotransferases. The addition of sodium chlorate to 20-day-old rat Sertoli cell cultures abolished [35S]-sulfate incorporation into neosynthesized PG and consequently reduced the residence time of undersulfated PG in cell membrane. Simultaneously, follicle-stimulating hormone (FSH)-stimulated estradiol synthesis was increased by 45%. The effects of sodium chlorate upon Sertoli cell PG synthesis and steroidogenesis were not reproduced with the addition of sodium chloride. Addition of phosphodiesterase inhibitors (MIX or Ro20-1724) decreased the magnitude of the chlorate effect on FSH-stimulated steroidogenesis, suggesting that part of chlorate's effect on steroidogenesis resulted from a decrease in adenosine cyclic 3',5'-phosphate (cAMP)-specific phosphodiesterase activity. Additionally, chlorate 1) increased Sertoli cell steroidogenesis at a step located beyond cAMP (restricted to Sertoli cell cultures exhibiting moderate steroidogenic response to (Bu)2cAMP) and 2) abolished the inhibition of steroidogenesis induced by transforming growth factor-beta. These results support our previous data, which showed that alteration in PG synthesis and the consequent decrease in cell membrane PG content induce an increase in FSH-stimulated estradiol synthesis in Sertoli cell cultures. The identification of cAMP-specific phosphodiesterase activity as a signal transduction step modified by PG undersulfation suggests the possible involvement of cell PG in the regulation of phosphodiesterase activity and, therefore, of FSH responsiveness during testicular development.
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PMID:Sodium chlorate induces undersulfation of cellular proteoglycans and increases in FSH-stimulated estradiol production in immature rat Sertoli cells. 1023 59


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