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)

Vasoactive intestinal peptide, secretin, catecholamines and prostaglandin E1 stimulate the accumulation of cyclic AMP in HT 29 cells (see Laburthe, M. et al. (1978) Proc. Natl. Acad. Sci. U.S. 75, 2772-2775). In the present work maximal activation of protein kinases has been obtained at similar or even lower concentrations of the effectors. Maximal stimulation also requires a phosphodiesterase inhibitor. Type I and type II cyclic AMP-dependent protein kinases from basal and stimulated cells have been characterized by DEAE-Sepharose chromatography. Further identidication of the kinase has been carried out by gel electrophoresis and assay of the enzymes in the gel slabs. Comparison of the radioautography patterns of high speed supernatant lysate from basal and stimulated cells shows: First, that one type I and two type II cyclic AMP-dependent protein kinases plus one or two major and two minor cyclic AMP-independent protein kinases are present in HT 29 cells. Second, that all three holoenzymes are fully dissociated upon maximal stimulation, while the activity of the independent kinases appears unchanged.
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PMID:Activation of cyclic AMP-dependent protein kinases in human gut adenocarcinoma (HT 29) cells in culture. 22 70

Vasoactive intestinal peptide (VIP) stimulated cyclic AMP production in rat peritoneal macrophages. The stimulatory effect of VIP was dependent on time, temperature and cell concentration, and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). At 15 degrees C, the response occurred in the 0.1-1000 nM range of VIP concentrations. Half maximal stimulation of cellular cyclic AMP (ED50) was obtained at 1.2 +/- 0.5 nM VIP, and maximal stimulation (about 3-fold basal level) was obtained between 100-1000 nM. The cyclic AMP system of rat peritoneal macrophages showed a high specificity for VIP. The order of potency observed in inducing cyclic AMP production was VIP greater than rGRF greater than hGRF greater than PHI greater than secretin. Glucagon, insulin, pancreastatin and octapeptide of cholecystokinin did not modify cyclic AMP levels at concentrations as high as 1 microM. The beta-adrenergic agonist isoproterenol increased the cyclic AMP production and show additive effect with VIP. Somatostatin inhibits the accumulation of cyclic AMP in the presence of both vasoactive intestinal peptide and isoproterenol. The finding of a VIP-stimulated cyclic AMP system in rat peritoneal macrophages, together with the previous characterization of high-affinity receptors for VIP in the same cell preparation, strongly suggest that VIP may be involved in the regulation of macrophage function.
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PMID:Stimulatory effect of vasoactive intestinal peptide (VIP) on cyclic AMP production in rat peritoneal macrophages. 137 99

Vasoactive intestinal peptide (VIP) was originally isolated from porcine duodenum and considered to be a gut hormone. Recent evidence indicates that it may also be involved in reproductive functions. In this study, a possible action of VIP on steroidogenesis by cultured testicular cells was investigated. Neonatal testicular cells were treated in vitro with hormones for 3 days and medium steroid or cAMP content was measured by radioimmunoassay. Treatment of cultured cells with VIP (10(-9) to 10(-6) M) increased the production of testosterone, progesterone, and pregnenolone in a dose-dependent fashion. Testosterone production in response to 10(-6) M VIP was about 5-10% of that maximally induced by LH. Addition of methyl-isobutyl-xanthine, a phosphodiesterase inhibitor, to the VIP-containing cultures significantly enhanced production of testosterone by 13-fold, of progesterone by 9-fold, and of pregnenolone by 2.5-fold as compared to treatment with VIP alone. Additional experiments also showed a dose-dependent stimulation of cAMP production by VIP. The VIP-related hormones PHM-27, secretin, and glucagon also stimulated progesterone and testosterone production with a potency order (PHM-27 greater than secretin greater than glucagon) consistent with that observed for other VIP receptor-mediated actions. A direct stimulatory effect of VIP on Leydig cells was indicated in studies on steroidogenesis by testicular cells separated on a metrizamide density gradient. In these studies, VIP stimulated androgen production in an LH-responsive subpopulation of testis cells but failed to affect steroid production in non-LH-responsive cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasoactive intestinal peptide stimulates androgen biosynthesis by cultured neonatal testicular cells. 243 Aug 45

Studies were conducted to evaluate the effects of vasoactive intestinal peptide (VIP) on steroidogenesis and plasminogen-activator (PA) activity in isolated granulosa cells of the largest preovulatory (F1) follicle of the hen. Vasoactive intestinal peptide, but not avian pancreatic polypeptide, the chicken VIP fragment (16-28) or the VIP congener, PHM-27, induced a dose-related increase in progesterone and androgen secretion, with an apparent median effective dose (ED50) of 5.9 X 10(-7) and 5.7 X 10(-7) M, respectively. The effects of VIP were, at least in part, mediated by the adenylyl cyclase system in that cotreatment of cells with VIP and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), potentiated the steroidogenic effects. However, the time course of action for VIP on steroidogenesis was considerably slower than that for the gonadotropin, luteinizing hormone (LH), and this was attributed to a slower induction of cyclic adenosine 3',5'-monophosphate (cAMP) formation within granulosa cells. Finally, VIP was found to be a potent inhibitor of PA activity, and this inhibition was potentiated by coincubation of VIP with IBMX. We suggest that, in the hen, VIP has a direct and specific action on both steroidogenesis and PA activity, and that these actions are mediated, at least in part, by the adenylyl cyclase system. The comparatively slow induction of cAMP formation by VIP suggests that this peptide is involved in the control of cell differentiation and development rather than the ovulatory process.
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PMID:Effects of vasoactive intestinal peptide on steroid secretion and plasminogen activator activity in granulosa cells of the hen. 245 37

Vasoactive intestinal peptide (VIP) is a putative neurotransmitter found in the salivary glands of many species, including the rat parotid gland. Parasympathetic denervation has been reported to deplete VIP in the rat parotid gland and to lead to supersensitivity to this peptide in vivo. We have compared the effects of VIP on acini isolated from parasympathetically denervated and unoperated parotid glands to examine possible supersensitivity to the peptide in vitro. VIP normally produced responses similar to those obtained with a low concentration of the beta adrenergic agonist isoproterenol (ISO), but strikingly different from the effects obtained with the muscarinic agonist carbachol (CARB). In parotid membrane preparations, VIP stimulated adenylate cyclase activity. Dissociated acini treated with VIP showed increases in cAMP accumulation and amylase release which were potentiated by forskolin and also by inhibition of phosphodiesterase. After parasympathetic denervation, maximal effects of VIP on adenylate cyclase, cAMP accumulation and amylase release in intact cells were increased two- to five-fold over contralateral control (or unoperated) parotid responses. The increase in adenylate cyclase-mediated responses after denervation was specific to VIP; there was no increased response nor increased sensitivity of any of these responses to ISO. Specific [125I]VIP binding to parotid acini increased two-fold per gland and three-fold per mg of protein after denervation; this probably explains the observed increases in the response to VIP.
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PMID:Parasympathetic denervation increases responses to VIP in isolated rat parotid acini. 247 29

Vasoactive intestinal peptide synergistically stimulated initiation of DNA synthesis in Swiss 3T3 cells. The peptide stimulated [3H]thymidine incorporation in the presence of insulin and either forskolin or an inhibitor of cAMP phosphodiesterase in a concentration-dependent manner. Half-maximal effect was obtained at 1 nM. At mitogenic concentrations, VIP stimulated a marked accumulation (eightfold) of cAMP. In contrast to other growth-promoting neuropeptides, VIP did not induce an increase in cytosolic free Ca2+ or an activation of protein kinase C. We conclude that neuropeptides can modulate long-term cell proliferation through multiple signaling pathways.
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PMID:Vasoactive intestinal peptide synergistically stimulates DNA synthesis in mouse 3T3 cells: role of cAMP, Ca2+, and protein kinase C. 283 26

Vasoactive intestinal peptide (VIP) is present in the rat ovary and has been shown to stimulate cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone production in cultured rat granulosa cells. In the present study, VIP-stimulated cAMP production has been studied in relation to steroid accumulation and oocyte maturation in isolated preovulatory rat follicles. VIP stimulated resumption of meiosis (oocyte maturation) in up to 60% of the follicle-enclosed oocytes after 6 h at 1 microM (control, 1.8%; luteinizing hormone 99%). The effect was time- and dose-dependent up to 6 h and was seen with both natural and synthetic VIP. VIP also stimulated the accumulation of steroids (estrogen, 2.3-fold; testosterone, 2.0-fold; and progesterone, 1.6-fold increase after 6 h of incubation) and lactate (2.6-fold) by the follicles. VIP-increased tissue levels of cAMP in the follicle were dose- and time-dependent. This effect was potentiated by a phosphodiesterase inhibitor. When isolated oocyte-cumulus complexes were studied, VIP caused a transient inhibition of spontaneous oocyte maturation, and demonstrated no effect on denuded oocytes. These results extend earlier preliminary observations on the ability of VIP to induce meiotic maturation of follicle-enclosed oocytes. Our results also show that VIP can stimulate steroid and lactate accumulation in the isolated follicles. The pattern of steroids produced suggests an effect both on the theca- and granulosa cells. We also show that VIP can delay spontaneous oocyte maturation. These effects appeared, at least partially, to be mediated by cAMP.
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PMID:Vasoactive intestinal peptide stimulates oocyte maturation, steroidogenesis, and cyclic adenosine 3',5'-monophosphate production in isolated preovulatory rat follicles. 284 82

The effects of certain peptides of the glucagon family on calmodulin activity were determined from their capacity to inhibit a calmodulin-dependent form of phosphodiesterase. Vasoactive intestinal peptide and secretin were potent inhibitors of calmodulin activity, having IC50 values of 0.5 microM and 2 microM, respectively. By contrast, glucagon failed to inhibit calmodulin activity even at concentrations of 100 microM. None of these compounds significantly inhibited the basal activity of phosphodiesterase at concentrations up to 100 microM. These findings support the suggestion that important structural features of peptides for anticalmodulin activity include a net positive charge and a hydrophobic surface.
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PMID:Inhibition of calmodulin-stimulated phosphodiesterase activity by vasoactive intestinal peptide. 298 33

Vasoactive intestinal peptide (VIP) and VIPergic nerve fibers are present in the ovaries of several mammalian species, suggesting a possible ovarian action of VIP. We have investigated the direct effects of synthetic porcine VIP on rat granulosa cell steroidogenesis in vitro. The cells were obtained from immature, hypophysectomized, estrogen-primed rats, and cultured in a serum-free medium for 24 h in the absence or presence of varying amounts of VIP. Medium steroids were then determined by specific radioimmunoassay. Vasoactive intestinal peptide dose-dependently stimulated progesterone, 20 alpha-hydroxypregn-4-ene-3-one (20 alpha-OH-progesterone), and estrogen production with an approximate ED50 value of 3 X 10(-8) M. Maximum steroid production induced by VIP ranged from 15% to 28% of that seen with maximal follicle-stimulating hormone (FSH) stimulation. In contrast to the ability of FSH to induce luteinizing hormone (LH) receptor formation, treatment with VIP did not increase [125I]iodo-human chorionic gonadotropin (hCG) binding to granulosa cells. The ability of several gastrointestinal peptides, having 17-44% sequence identity to VIP, to stimulate granulosa cell steroidogenesis was also tested. The most closely related peptide, PHM-27 was less effective than VIP, and the least closely related, secretin and glucagon, were ineffective at 10(-6) M. Vasoactive intestinal peptide seems to act at least partly through cyclic 3',5'-adenosine monophosphate (cAMP)-dependent processes: addition of a phosphodiesterase inhibitor significantly potentiated the VIP stimulation of granulosa cell steroidogenesis, and VIP was capable of producing a dose- and time-dependent increase in both intracellular and medium cAMP levels. Vasoactive intestinal peptide stimulation of estrogen production seemed to be a result of increased aromatase activity. The increased progesterone production was associated with increased pregnenolone production, increased rate of conversion of pregnenolone to progesterone via 3 beta-hydroxysteroid dehydrogenase, and decreased metabolism of progesterone via 20 alpha-hydroxysteroid dehydrogenase. These results indicate that VIP exerts a specific action on granulosa cells to increase estrogen and progestin production. The observed direct effects of VIP, coupled with its identification in the ovary, suggest that VIP may be a physiologically important regulator of ovarian activity.
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PMID:Vasoactive intestinal peptide: a novel stimulator of steroidogenesis by cultured rat granulosa cells. 299 97

Vasoactive intestinal peptide stimulated cyclic AMP-dependent protein kinase activity in human blood mononuclear cells. The simultaneous presence of a phosphodiesterase inhibitor was required to elicit maximal activation. The apparent Ka value of half the maximal stimulation was about 60 pmol. Secretin exhibited a 170-times lower potency. Other peptides such as glucagon or insulin had no effect even at 1 microM.
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PMID:Activation of cyclic AMP-dependent protein kinase by VIP in blood mononuclear cells. 620 83


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